COVID-19 vaccine

COVID-19 vaccination doses administered per 100 people
Map of countries by approval status
  Approved for general use, mass vaccination underway
  EUA (or equivalent) granted, mass vaccination underway
  EUA granted, limited vaccination
  Approved for general use, mass vaccination planned
  EUA granted, mass vaccination planned
  EUA pending
  No data available

A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus causing coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, there was an established body of knowledge about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which enabled accelerated development of various vaccine technologies during early 2020.[1] On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.[2]

In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of April 2021, 14 vaccines are authorized by at least one national regulatory authority for public use: two RNA vaccines (Pfizer–BioNTech and Moderna), five conventional inactivated vaccines (BBIBP-CorV, CoronaVac, Covaxin, WIBP-CorV and CoviVac), five viral vector vaccines (Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Johnson & Johnson), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer).[3][failed verification] In total, as of March 2021, 308 vaccine candidates are in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.[3]

Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers.[4] Single dose interim use is under consideration in order to extend vaccination to as many people as possible until vaccine availability improves.[5][6][7][8]

As of 9 May 2021, 1.3 billion doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies.[9] AstraZeneca anticipates producing 3 billion doses in 2021, Pfizer–BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidecia 500 million doses in 2021.[10][11] By December 2020, more than ten billion vaccine doses had been preordered by countries,[12] with about half of the doses purchased by high-income countries comprising 14% of the world's population.[13]

Background

A CDC Fact sheet about COVID-19 vaccines
A US airman receiving a COVID-19 vaccine

Prior to COVID‑19, a vaccine for an infectious disease had never been produced in less than several years – and no vaccine existed for preventing a coronavirus infection in humans.[14] However, vaccines have been produced against several animal diseases caused by coronaviruses, including (as of 2003) infectious bronchitis virus in birds, canine coronavirus, and feline coronavirus.[15] Previous projects to develop vaccines for viruses in the family Coronaviridae that affect humans have been aimed at severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Vaccines against SARS[16] and MERS[17] have been tested in non-human animals.

According to studies published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world at that time.[18][19][20] As of 2020, there is no cure or protective vaccine proven to be safe and effective against SARS in humans.[21][22] There is also no proven vaccine against MERS.[23] When MERS became prevalent, it was believed that existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection.[21][24] As of March 2020, there was one (DNA based) MERS vaccine which completed Phase I clinical trials in humans[25] and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).[26]

Planning and development

Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[27] According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development puts North American entities having about 40% of the activity compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.[27][28]

Multiple steps along the entire development path are evaluated, including:[14][29]

  • the level of acceptable toxicity of the vaccine (its safety),
  • targeting vulnerable populations,
  • the need for vaccine efficacy breakthroughs,
  • the duration of vaccination protection,
  • special delivery systems (such as oral or nasal, rather than by injection),
  • dose regimen,
  • stability and storage characteristics,
  • emergency use authorization before formal licensing,
  • optimal manufacturing for scaling to billions of doses, and
  • dissemination of the licensed vaccine.

Challenges

There have been several unique challenges with COVID-19 vaccine development.

The urgency to create a vaccine for COVID‑19 led to compressed schedules that shortened the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process typically conducted sequentially over years.[30]

Timelines for conducting clinical research – normally a sequential process requiring years – are being compressed into safety, efficacy, and dosing trials running simultaneously over months, potentially compromising safety assurance.[30][31] As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020,[32] and by March were pursuing numerous candidates on short timelines, with the goal to showcase Chinese technology strengths over those of the United States, and to reassure the Chinese people about the quality of vaccines produced in China.[30][33]

The rapid development and urgency of producing a vaccine for the COVID‑19 pandemic may increase the risks and failure rate of delivering a safe, effective vaccine.[28][34][35] Additionally, research at universities is obstructed by physical distancing and closing of laboratories.[36][37]

Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels and adverse effects of the candidate vaccine.[38][39] Vaccine developers have to invest resources internationally to find enough participants for Phase II–III clinical trials when the virus has proved to be a "moving target" of changing transmission rate across and within countries, forcing companies to compete for trial participants;[40] clinical trial organizers may encounter people unwilling to be vaccinated due to vaccine hesitancy[41] or disbelieving the science of the vaccine technology and its ability to prevent infection.[42] Even as new vaccines are developed during the COVID‑19 pandemic, licensure of COVID‑19 vaccine candidates requires submission of a full dossier of information on development and manufacturing quality.[43][44][45]

Organizations

Internationally, the Access to COVID-19 Tools Accelerator is a G20 and World Health Organization (WHO) initiative announced in April 2020.[46][47] It is a cross-discipline support structure to enable partners to share resources and knowledge. It comprises four pillars, each managed by two to three collaborating partners: Vaccines (also called "COVAX"), Diagnostics, Therapeutics, and Health Systems Connector.[48] The WHO's April 2020 "R&D Blueprint (for the) novel Coronavirus" documented a "large, international, multi-site, individually randomized controlled clinical trial" to allow "the concurrent evaluation of the benefits and risks of each promising candidate vaccine within 3–6 months of it being made available for the trial." The WHO vaccine coalition will prioritize which vaccines should go into Phase II and III clinical trials, and determine harmonized Phase III protocols for all vaccines achieving the pivotal trial stage.[49]

National governments have also been involved in vaccine development. Canada announced funding for 96 research vaccine research projects at Canadian companies and universities, with plans to establish a "vaccine bank" that could be used if another coronavirus outbreak occurs,[50] and to support clinical trials and develop manufacturing and supply chains for vaccines.[51] China provided low-rate loans to a vaccine developer through its central bank and "quickly made land available for the company" to build production plants.[31] Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing.[52] Great Britain formed a COVID‑19 vaccine task force in April 2020 to stimulate local efforts for accelerated development of a vaccine through collaborations of industry, universities, and government agencies. It encompassed every phase of development from research to manufacturing.[53] In the United States, the Biomedical Advanced Research and Development Authority (BARDA), a federal agency funding disease-fighting technology, announced investments to support American COVID‑19 vaccine development and manufacture of the most promising candidates.[31][54] In May 2020, the government announced funding for a fast-track program called Operation Warp Speed.[55][56]

Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), formed alliances with biotechnology companies, governments, and universities to accelerate progression to an effective vaccine.[31][30]

History

COVID‑19 vaccine research samples in a NIAID lab freezer (30 January 2020)

After the coronavirus was isolated in late 2019,[57] its genetic sequence was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten development of a preventive COVID-19 vaccine.[58][59][60] Since early 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[61] By June 2020, tens of billions of dollars were invested by corporations, governments, international health organizations, and university research groups to develop dozens of vaccine candidates and prepare for global vaccination programs to immunize against COVID‑19 infection.[59][62][63][64] According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development puts North American entities having about 40% of the activity compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.[58][61]

In February 2020, the WHO said it did not expect a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the causative virus, to become available in less than 18 months.[65] The rapidly growing infection rate of COVID‑19 worldwide during early 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines,[66] with four vaccine candidates entering human evaluation in March (see the table of clinical trials started in 2020, below).[58][67]

On 24 June 2020, China approved the CanSino vaccine for limited use in the military and two inactivated virus vaccines for emergency use in high-risk occupations.[68] On 11 August 2020, Russia announced the approval of its Sputnik V vaccine for emergency use, though one month later only small amounts of the vaccine had been distributed for use outside of the phase 3 trial.[69]

The Pfizer–BioNTech partnership submitted an EUA request to the FDA for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020.[70][71] On 2 December 2020, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine,[72][73] becoming the first country to approve this vaccine and the first country in the Western world to approve the use of any COVID‑19 vaccine.[74][75][76] As of 21 December, many countries and the European Union[77] have authorized or approved the Pfizer–BioNTech COVID‑19 vaccine. Bahrain and the United Arab Emirates granted emergency marketing authorization for BBIBP-CorV, manufactured by Sinopharm.[78][79] On 11 December 2020, the United States Food and Drug Administration (FDA) granted an Emergency Use Authorization (EUA) for the Pfizer–BioNTech COVID‑19 vaccine.[80] A week later, they granted an EUA for mRNA-1273, the Moderna vaccine.[81][82][83][84]

On March 31, 2021, the Russian government announced that they had registered the first COVID-19 vaccine for animals.[85][86][87][88][89]

Vaccine types

Conceptual diagram showing three vaccine types for forming SARS‑CoV‑2 proteins to prompt an immune response: (1) RNA vaccine, (2) subunit vaccine, (3) viral vector vaccine
Vaccine platforms being employed for SARS-CoV-2. Whole virus vaccines include both attenuated and inactivated forms of the virus. Protein and peptide subunit vaccines are usually combined with an adjuvant in order to enhance immunogenicity. The main emphasis in SARS-CoV-2 vaccine development has been on using the whole spike protein in its trimeric form or components of it, such as the RBD region. Multiple non-replicating viral vector vaccines have been developed, particularly focused on adenovirus; while there has been less emphasis on the replicating viral vector constructs.[90]

As of January 2021, nine different technology platforms – with the technology of numerous candidates remaining undefined – are under research and development to create an effective vaccine against COVID‑19.[3][27] Most of the platforms of vaccine candidates in clinical trials are focused on the coronavirus spike protein and its variants as the primary antigen of COVID‑19 infection.[27] Platforms being developed in 2020 involved nucleic acid technologies (nucleoside-modified messenger RNA and DNA), non-replicating viral vectors, peptides, recombinant proteins, live attenuated viruses, and inactivated viruses.[14][27][28][34]

Many vaccine technologies being developed for COVID‑19 are not like vaccines already in use to prevent influenza, but rather are using "next-generation" strategies for precision on COVID‑19 infection mechanisms.[27][28][34] Several of the synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an immune response to the virus before it attaches to a human cell.[91] Vaccine platforms in development may improve flexibility for antigen manipulation and effectiveness for targeting mechanisms of COVID‑19 infection in susceptible population subgroups, such as healthcare workers, the elderly, children, pregnant women, and people with existing weakened immune systems.[27][28]

RNA vaccines

Diagram of the operation of an RNA vaccine. Messenger RNA contained in the vaccine enters cells and is translated into foreign proteins, which trigger an immune response.

An RNA vaccine contains RNA which, when introduced into a tissue, acts as messenger RNA (mRNA) to cause the cells to build the foreign protein and stimulate an adaptive immune response which teaches the body how to identify and destroy the corresponding pathogen or cancer cells. RNA vaccines often, but not always, use nucleoside-modified messenger RNA. The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles which protect the RNA strands and help their absorption into the cells.[92][93][94][95]

RNA vaccines were the first COVID-19 vaccines to be authorized in the United States and the European Union.[96][97] As of January 2021, authorized vaccines of this type are the Pfizer–BioNTech COVID-19 vaccine[98][99][100] and the Moderna COVID-19 vaccine.[101][102] As of February 2021, the CVnCoV RNA vaccine from CureVac is awaiting authorization in the EU.[103]

Severe allergic reactions are rare. In December 2020, 1,893,360 first doses of Pfizer–BioNTech COVID‑19 vaccine administration resulted in 175 cases of severe allergic reaction, of which 21 were anaphylaxis.[104] For 4,041,396 Moderna COVID-19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported.[104] The lipid nanoparticles were most likely responsible for the allergic reactions.[104]

Adenovirus vector vaccines

These vaccines are examples of non-replicating viral vector vaccines, using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein.[105][106] The viral vector-based vaccines against COVID-19 are non-replicating, meaning that they do not make new virus particles, but rather produce only the antigen which elicits a systemic immune response.[105]

As of January 2021, authorized vaccines of this type are the Oxford–AstraZeneca COVID-19 vaccine,[107][108][109] the Sputnik V COVID-19 vaccine,[110] Convidecia, and the Johnson & Johnson COVID-19 vaccine.[111][112]

Convidecia and the Johnson & Johnson COVID-19 vaccine are both one-shot vaccines which offer less complicated logistics and can be stored under ordinary refrigeration for several months.[113][114]

The Sputnik V COVID-19 vaccine uses Ad26 for the first dose, which is the same as the Johnson & Johnson vaccine's only dose, and Ad5 for the second dose. Convidecia uses Ad5 for its only dose.[115]

Inactivated virus vaccines

Inactivated vaccines consist of virus particles that have been grown in culture and then are killed using a method such as heat or formaldehyde to lose disease producing capacity, while still stimulating an immune response.[116]

As of January 2021, authorized vaccines of this type are the Chinese CoronaVac,[117][118][119] BBIBP-CorV,[120] and WIBP-CorV; the Indian Covaxin; and the Russian CoviVac.[121] Vaccines in clinical trials include the Valneva COVID-19 vaccine.[122][123]

Subunit vaccines

Subunit vaccines present one or more antigens without introducing whole pathogen particles. The antigens involved are often protein subunits, but can be any molecule that is a fragment of the pathogen.[124]

As of April 2021, the two authorized vaccines of this type are the peptide vaccine EpiVacCorona[125] and RBD-Dimer.[3] Vaccines with pending authorizations include the Novavax COVID-19 vaccine,[126] SOBERANA 02 (a conjugate vaccine), and the Sanofi–GSK vaccine. The V451 vaccine was previously in clinical trials, which were terminated because it was found that the vaccine may potentially cause incorrect results for subsequent HIV testing.[127][128]

Other types

Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines,[129][130][131][132][133][134] at least two lentivirus vector vaccines,[135][136] a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.[137]

Oral vaccines and intranasal vaccines are being developed and studied.[138]

Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID‑19 infection.[139] There is experimental evidence that the BCG vaccine for tuberculosis has non-specific effects on the immune system, but no evidence that this vaccine is effective against COVID‑19.[140]

Efficacy

Cumulative incidence curves for symptomatic COVID‑19 infections after the first dose of the Pfizer–BioNTech vaccine (tozinameran) or placebo in a double-blind clinical trial. (red: placebo; blue: tozinameran)[141]

Vaccine efficacy is the risk of getting the disease by vaccinated participants in a controlled trial compared with the risk of getting the disease by unvaccinated participants.[142] An efficacy of 0% means that the vaccine does not work (identical to placebo). An efficacy of 50% means that there are half as many cases of infection as in unvaccinated individuals.

It is not straightforward to compare the efficacies of the different vaccines because the trials were run with different populations, geographies, and variants of the virus.[143] In the case of COVID‑19, a vaccine efficacy of 67% may be enough to slow the pandemic, but this assumes that the vaccine confers sterilizing immunity, which is necessary to prevent transmission. Vaccine efficacy reflects disease prevention, a poor indicator of transmissibility of SARS‑CoV‑2 since asymptomatic people can be highly infectious.[144] The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) set a cutoff of 50% as the efficacy required to approve a COVID‑19 vaccine.[145][146] Aiming for a realistic population vaccination coverage rate of 75%, and depending on the actual basic reproduction number, the necessary effectiveness of a COVID-19 vaccine is expected to need to be at least 70% to prevent an epidemic and at least 80% to extinguish it without further measures, such as social distancing.[147]

In efficacy calculations, symptomatic COVID-19 is generally defined as having both a positive PCR test and at least one or two of a defined list of COVID-19 symptoms, although exact specifications vary between trials.[citation needed] The trial location also affects the reported efficacy because different countries have different prevalences of SARS-CoV-2 variants.[citation needed] Ranges below are 95% confidence intervals unless indicated otherwise, and all values are for all participants regardless of age, according to the references for each of the trials. By definition, the absence of a confidence interval means that the accuracy of the estimates without an associated confidence interval is unknown to the public. Efficacy against severe COVID-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority.[148] Authorized and approved vaccines have shown the following efficacies:

Vaccine Efficacy by severity of COVID-19 Trial location Refs
Mild or moderate[A] Severe without hospitalization or death[B] Severe with hospitalization or death[C]
Moderna 94% (8997%)[D] 100%[E] 100%[E] United States [149]
Pfizer–BioNTech 95% (9098%)[F] Not reported Not reported Multinational [150]
Sputnik Light 79% Not reported Not reported Russia [151][unreliable medical source?]
Sputnik V 92% (8695%) 100% (94100%) 100% Russia [152]
Oxford–AstraZeneca 81% (6091%)[G] 100% (97.5% CI, 72100%) 100% Multinational [153]
76% (6882%)[H] 100% 100% United States [154]
BBIBP-CorV 79%[I] 100%[155][unreliable medical source?] 100%[155][unreliable medical source?] Multinational [156][unreliable medical source?]
CoronaVac 78%[I] 84% (5894%)[I] 100% (56100%)[I] Brazil [157][158][159][unreliable medical source?]
Novavax 89% (7595%) 100%[J] 100%[J] United Kingdom [160][161]
60% (2080%) 100%[J] 100%[J] South Africa
Johnson & Johnson 66% (5575%)[K][L] 85% (5497%)[L] 100%[L][M] Multinational [162]
72% (5882%)[K][L] 86% (−9 to 100%)[L] 100%[L][M] United States
68% (4981%)[K][L] 88% (8100%)[L] 100%[L][M] Brazil
64% (4179%)[K][L] 82% (4695%)[L] 100%[L][M] South Africa
Covaxin 78% (6188%)[I] 100%[I] 100%[I] India [164][165][unreliable medical source?]
Convidecia 66%[I] 91%[I] Not reported Multinational [166][unreliable medical source?]
  1. ^ Mild symptoms: fever, dry cough, fatigue, myalgia, arthralgia, sore throat, diarrhea, nausea, vomiting, headache, anosmia, ageusia, nasal congestion, rhinorrhea, conjunctivitis, skin rash, chills, dizziness. Moderate symptoms: mild pneumonia.
  2. ^ Severe symptoms without hospitalization or death for an individual, are any one of the following severe respiratory symptoms measured at rest on any time during the course of observation (on top of having either pneumonia, deep vein thrombosis, dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °C (100 °F)), that however were not persistent/severe enough to cause hospitalization or death: Any respiratory rate ≥30 breaths/minute, heart rate ≥125 beats/minute, oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg.
  3. ^ Severe symptoms causing hospitalization or death, are those requiring treatment at hospitals or results in deaths: dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °C (100 °F), respiratory failure, kidney failure, multiorgan dysfunction, sepsis, shock.
  4. ^ Mild/Moderate COVID-19 symptoms observed in the Moderna vaccine trials, were only counted as such for vaccinated individuals if they began more than 14 days after their second dose, and required presence of a positive RT-PCR test result along with at least two systemic symptoms (fever above 38ºC, chills, myalgia, headache, sore throat, new olfactory and taste disorder) or just one respiratory symptom (cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia).[149]
  5. ^ a b Severe COVID-19 symptoms observed in the Moderna vaccine trials, were defined as symptoms having met the criteria for mild/moderate symptoms plus any of the following observations: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS, (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure <90 mmHg, diastolic BP <60 mmHg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death. No severe cases were detected for vaccinated individuals in the trials, compared with thirty in the placebo group (incidence rate 9.1 per 1000 person-years).[149]
  6. ^ Mild/Moderate COVID-19 symptoms observed in the Pfizer–BioNTech vaccine trials, were only counted as such for vaccinated individuals if they began more than seven days after their second dose, and required presence of a positive RT-PCR test result along with at least one of the following symptoms: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; or vomiting.[150]
  7. ^ With twelve weeks or more between doses. For an interval of less than six weeks, the trial found an efficacy ≈55% (3370%).
  8. ^ With a four-week interval between doses. Efficacy is "at preventing symptomatic COVID-19".
  9. ^ a b c d e f g h i These Phase III data have not been published or peer reviewed.
  10. ^ a b c d No cases detected in trial.
  11. ^ a b c d Moderate cases.
  12. ^ a b c d e f g h i j k l Efficacy reported 28 days post-vaccination for the Johnson & Johnson single shot vaccine. A lower efficacy was found for the vaccinated individuals 14 days post-vaccination.[162]
  13. ^ a b c d No hospitalizations or deaths were detected 28 days post-vaccination for 19,630 vaccinated individuals in the trials, compared with 16 hospitalizations reported in the placebo group of 19,691 individuals (incidence rate 5.2 per 1000 person-years)[162] and seven COVID-19 related deaths for the same placebo group.[163]

Effectiveness

The real-world studies of vaccine effectiveness measure to which extent a certain vaccine has succeeded in preventing COVID-19 infection, symptoms, hospitalization and death for the vaccinated individuals in a large population under routine conditions that are less than ideal.[167]

  • In Israel, among the 715,425 individuals vaccinated by the Moderna or Pfizer-BioNTech vaccines during the period 20 December 2020, to 28 January 2021, it was observed for the period starting seven days after the second shot, that only 317 people (0.04%) became sick with mild/moderate Covid-19 symptoms and only 16 people (0.002%) were hospitalized.[168]
  • The Pfizer-BioNTech and Moderna Covid-19 vaccines provide highly effective protection, according to a report from the US Centers for Disease Control and Prevention. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%.[169]
  • 15,121 health care workers from 104 hospitals in England, that all had tested negative for COVID-19 antibodies prior of the study, were followed by RT-PCR tests twice a week from 7 December 2020 to 5 February 2021, during a time when lineage B.1.1.7 was in circulation as the dominant variant. The study compared the positive results for the 90.7% vaccinated share of their cohort with the 9.3% unvaccinated share, and found that the Pfizer-BioNTech vaccine reduced all infections (including asymptomatic), by 72% (58-86%) three weeks after the first dose and 86% (76-97%) one week after the second dose.[170]
  • A study of the general population in Israel conducted from 17 January to 6 March 2021, during a time when lineage B.1.1.7 was in circulation as the dominant variant, found that the Pfizer vaccine reduced asymptomatic COVID-19 infections by 94% and symptomatic COVID-19 infections by 97%.[171]
  • A study, among pre-surgical patients across the Mayo Clinic system in the United States, showed that mRNA vaccines were 80% protective against asymptomatic infections.[172]
  • The director of the China Center for Disease Control, Gao Fu, admitted that Chinese vaccines "don't have very high protection rates" at a conference held on 10 April 2021. The CoronaVac vaccine developed by Sinovac, a private company, was found to have an efficacy rate of just 50.4% in clinical trials in Brazil. Another trial in Turkey showed it was 83.5% effective. State-owned Sinopharm said its two vaccines have efficacy rates of 79.4% and 72.5%.[173]
Vaccine Effectiveness by severity of COVID-19 Study location Refs
Asymptomatic Symptomatic Death
Pfizer–BioNTech 86% (7697%) Not reported United Kingdom [170]
90% (6897%) 100%[i] United States [169]
94% 97% Israel [171]
Moderna 90% (6897%) 100%[i] United States [169]
CoronaVac Not reported 67% (6569%) 80% (7386%) Chile [174][175][176][177]
Sputnik V Not reported 98% Not reported Russia [178][179]
  1. ^ a b No cases detected in study.

Variants

World Health Organization video describing how variants proliferate in unvaccinated areas.

The potential emergence of a SARS-CoV-2 variant that is moderately or fully resistant to the antibody response elicited by the current generation of COVID-19 vaccines may necessitate modification of the vaccines.[180] Trials indicate many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19.[181] As of February 2021, the US Food and Drug Administration believed that all FDA authorized vaccines remained effective in protecting against circulating strains of SARS-CoV-2.[180]

B.1.1.7 variant

In December 2020, a new SARS‑CoV‑2 variant, B.1.1.7, was identified in the UK.[182]

Early results suggest protection to the UK variant from the Pfizer-BioNTech and Moderna vaccines.[183][184]

One study indicated that the Oxford–AstraZeneca COVID-19 vaccine had an efficacy of 42–89% against the B.1.1.7 variant, versus 71–91% against non-B.1.1.7 variants.[185]

Preliminary data from a clinical trial indicates that the Novavax vaccine is ~96% effective for symptoms against the original variant and~86% against B.1.1.7.[186]

An April 2021 letter to The New England Journal of Medicine stated that the level of neutralization for the CoronaVac vaccine against B.1.1.7 is 50% effective in comparaison with the original Wuhan strain.[187] For comparaison, in the same study they analyzed that convalescents' (~5 months since contraction) B.1.1.7 neutralization was "similar" to Wuhan strain.[187]

501.V2 variant

Moderna has launched a trial of a vaccine to tackle the South African 501.V2 variant (also known as B.1.351).[188] On 17 February 2021, Pfizer announced neutralization activity was reduced by two-thirds for the 501.V2 variant, while stating that no claims about the efficacy of the vaccine in preventing illness for this variant could yet be made.[189] Decreased neutralizing activity of sera from patients vaccinated with the Moderna and Pfizer-BioNTech vaccines against B.1.351 was latter confirmed by several studies.[184][190] On 1 April 2021, an update on a Pfizer/BioNTech South African vaccine trial stated that the vaccine was 100% effective so far (i.e., vaccinated participants saw no cases), with six of nine infections in the placebo control group being the B.1.351 variant.[191]

In January 2021, Johnson & Johnson, which held trials for its Ad26.COV2.S vaccine in South Africa, reported the level of protection against moderate to severe COVID-19 infection was 72% in the United States and 57% in South Africa.[192]

On 6 February 2021, the Financial Times reported that provisional trial data from a study undertaken by South Africa's University of the Witwatersrand in conjunction with Oxford University demonstrated reduced efficacy of the Oxford–AstraZeneca COVID-19 vaccine against the 501.V2 variant.[193] The study found that in a sample size of 2,000 the AZD1222 vaccine afforded only "minimal protection" in all but the most severe cases of COVID-19.[194] On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of about a million doses of the vaccine whilst they examine the data and await advice on how to proceed.[195][196]

In March 2021, it was reported that the "preliminary efficacy" of the Novavax vaccine (NVX-CoV2373) against B.1.351 for mild, moderate, or severe COVID-19[197] for HIV-negative participants is 51%.[198]

In April 2021, it was reported that the level of neutralization for the CoronaVac vaccine was only 30% effective in comparison with the original Wuhan strain. For comparison, in the same study they analyzed that convalescents' (~5 months since contraction) B.1.351 neutralization was 50% effective.[199]

P1 variant

The P1 variant (also known as 20J/501Y.V3), initially identified in Brazil, seems to partially escape vaccination with the Pfizer-BioNTech vaccine.[190]

B.1.617 variant

In October 2020, a new double-mutation variant was discovered in India, which was named B.1.617. There were very few detections until January 2021 and by April it had spread to at least 20 countries in all continents except Antarctica and South America.[200][201][202] Among some 15 defining mutations, it has spike mutations D111D (synonymous), G142D,[203] P681R, E484Q[204] and L452R,[205] the latter two of which may cause it to easily avoid antibodies.[206] In an update on 15 April 2021, PHE designated B.1.617 as a 'Variant under investigation', VUI-21APR-01.[207]

Trial and authorization status

Phase I trials test primarily for safety and preliminary dosing in a few dozen healthy subjects, while Phase II trials – following success in Phase I – evaluate immunogenicity, dose levels (efficacy based on biomarkers) and adverse effects of the candidate vaccine, typically in hundreds of people.[38][39] A Phase I–II trial consists of preliminary safety and immunogenicity testing, is typically randomized, placebo-controlled, while determining more precise, effective doses.[39] Phase III trials typically involve more participants at multiple sites, include a control group, and test effectiveness of the vaccine to prevent the disease (an "interventional" or "pivotal" trial), while monitoring for adverse effects at the optimal dose.[38][39] Definition of vaccine safety, efficacy, and clinical endpoints in a Phase III trial may vary between the trials of different companies, such as defining the degree of side effects, infection or amount of transmission, and whether the vaccine prevents moderate or severe COVID‑19 infection.[40][208][209]

A clinical trial design in progress may be modified as an "adaptive design" if accumulating data in the trial provide early insights about positive or negative efficacy of the treatment.[210][211] Adaptive designs within ongoing Phase II–III clinical trials on candidate vaccines may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, avoiding duplication of research efforts, and enhancing coordination of design changes for the Solidarity trial across its international locations.[210][212]

List of authorized and approved vaccines

National regulatory authorities have granted emergency use authorizations for thirteen vaccines. Six of those have been approved for emergency or full use by at least one WHO-recognized stringent regulatory authority.

Vaccines authorized for emergency use or approved for full use
Vaccine, developers/sponsors Country of origin Type (technology) Doses, interval Storage temperature Current phase (participants) Authorization
Oxford–AstraZeneca COVID-19 vaccine (Vaxzevria, Covishield)[213][a][b][107][108][109]
University of Oxford, AstraZeneca, CEPI
United Kingdom, Sweden Adenovirus vector (ChAdOx1)[107] 2 doses
4–12 weeks[217]
2–8 °C[218] Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity.[219]
Overall efficacy of 76% after the first dose and 81% after a second dose taken 12 weeks or more after the first.[153]
May 2020 – Aug 2021, Brazil (5,000),[220] United Kingdom, India[221]
Full (2)
Emergency (143)
Pfizer–BioNTech COVID-19 vaccine (Comirnaty)[98][99][100]
BioNTech, Pfizer
United States, Germany RNA (modRNA in lipid nanoparticles)[98] 2 doses
3–4 weeks[222][c]
−70±10 °C[d]
(ULT)
Phase III (43,448)
Randomized, placebo-controlled.
Positive results from an interim analysis were announced on 18 November 2020[227] and published on 10 December 2020 reporting an overall efficacy of 95%.[228][229]
Jul–Nov 2020,[230][142] Germany, United States
Full (5)
Emergency (95)
Sputnik V COVID-19 vaccine (Gam-COVID-Vac)
Gamaleya Research Institute of Epidemiology and Microbiology
Russia Adenovirus vector (recombinant Ad5 and Ad26)[231] 2 doses
3 weeks[232]
−18 °C[e]
(freezer)
Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety.[234]
Interim analysis from the trial was published in The Lancet, indicating 91.6% efficacy without unusual side effects.[152]
Aug 2020 – May 2021, Russia, Belarus,[235] India,[236][237] Venezuela,[238][239] UAE[240]
Full (2)
Emergency (66)
Moderna COVID-19 vaccine[101][102]
Moderna, NIAID, BARDA, CEPI
United States RNA (modRNA in lipid nanoparticles)[241] 2 doses
4 weeks[242][c]
−20±5 °C[243]
(freezer)
Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity.
Positive results from an interim analysis were announced on 15 November 2020[244] and published on 30 December 2020 reporting an overall efficacy of 94%.[245]
Jul 2020 – Oct 2022, United States
Full (2)
Emergency (50)
BBIBP-CorV[120]
Sinopharm: Beijing Institute of Biological Products
China Inactivated SARS‑CoV‑2 (vero cells)[120] 2 doses
3–4 weeks[246]
2–8 °C[247] Phase III (48,000)
Randomized, double-blind, parallel placebo-controlled, to evaluate safety and protective efficacy.
Sinopharm's internal analysis indicated a 79% efficacy.[248]
Jul 2020 – Jul 2021, United Arab Emirates, Bahrain, Jordan,[249] Argentina,[250] Morocco,[251] Peru[252]
Full (4)
Emergency (50)
Johnson & Johnson COVID-19 vaccine[111][112]
Janssen Vaccines (Johnson & Johnson), BIDMC
United States, Netherlands Adenovirus vector (recombinant Ad26)[253] 1 dose[254] 2–8 °C[254] Phase III (40,000)
Randomized, double-blinded, placebo-controlled
Positive results from an interim analysis were announced on 29 January 2021. J&J reports an efficacy of 66% against mild and moderate symptoms, and 85% against severe symptoms. Further, the mild and moderate efficacy ranged from 64% in South Africa to 72% in the United States.[255][162]
Jul 2020 – ? 2023, United States, Argentina, Brazil, Chile, Colombia, Mexico, Peru, the Philippines, South Africa, Ukraine
Full (0)
Emergency (46)
CoronaVac[117][118][119]
Sinovac
China Inactivated SARS‑CoV‑2 (vero cells)[117] 2 doses
2–3 weeks[256][257]
2–8 °C[258] Phase III (33,620)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
Final Phase III results from Turkey showed an efficacy of 83.5%.[259] A Chilean study showed 67% efficacy against symptoms, reduced hospitalizations by 85%, intensive care visits by 89%, and deaths by 80%.[260] Brazil announced results showing 50.7% effective at preventing symptomatic infections, 83.7% effective in preventing mild cases, and 100% effective in preventing severe cases.[261]
July 2020 – Oct 2021, Brazil (15,000);[262] Aug 2020 – January 2021, Indonesia (1,620); Chile (3,000);[263] Turkey (13,000)[264]
Full (1)
Emergency (32)
BBV152 (Covaxin)
Bharat Biotech, Indian Council of Medical Research
India Inactivated SARS‑CoV‑2 (vero cells)[265] 2 doses
4 weeks[266]
2–8 °C[266] Phase III (25,800)
Randomised, observer-blinded, placebo-controlled[267]
The interim efficacy rate is 81% as per third phase trial.[268] All data from the animal, first, second phase trials have been made public through peer-reviewed journals.[269] Phase III trials had shown 81% efficacy.[270]
Nov 2020 – Mar 2021, India.
Full (0)
Emergency (14)
Ad5-nCoV (Convidecia)
CanSino Biologics, Beijing Institute of Biotechnology of the Academy of Military Medical Sciences
China Adenovirus vector (recombinant Ad5)[271] 1 dose[166] 2–8 °C[166] Phase III (40,000)
Global multi-center, randomized, double-blind, placebo-controlled to evaluate efficacy, safety and immunogenicity.
In February 2021, interim analysis from global trials showed an efficacy of 65.7% against moderate cases of COVID-19 and 90.98% efficacy against severe cases.[166]
Mar–Dec 2020, China; Sep 2020 – Dec 2021, Pakistan; Sep–Nov 2020, Russia,[272] China, Argentina, Chile;[273] Mexico;[274] Pakistan;[275] Saudi Arabia[276][277]
Full (1)
Emergency (5)
EpiVacCorona[278][279]
Vector Institute
Russia Subunit (peptide)[278] 2 doses
3 weeks[278]
2–8 °C[280] Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety
Nov 2020 – Dec 2021, Russia[281]
Full (1)
Emergency (2)
ZF2001 (RBD-Dimer)[3]
Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.
China Subunit (recombinant) 3 doses
30 days[282][283]
2–8 °C[284] Phase III (29,000)
Randomized, double-blind, placebo-controlled[282]
Dec 2020 – Apr 2022, China, Ecuador, Indonesia, Malaysia, Pakistan, Uzbekistan[285][286]
Full (0)
Emergency (2)
WIBP-CorV
Sinopharm: Wuhan Institute of Biological Products
China Inactivated SARS‑CoV‑2 (vero cells) 2 doses[287][288][289] 2–8 °C Phase III (51,600)
Randomized, double-blind, placebo-controlled[290]
Jul 2020 – Mar 2021, Bahrain, Egypt, Jordan, United Arab Emirates;[287] Sep 2020 – Sep 2021, Peru;[288] Sep 2020 – Dec 2020, Morocco[291]
Full (0)
Emergency (2)
CoviVac[292]
The Chumakov Centre at the Russian Academy of Sciences
Russia Inactivated SARS‑CoV‑2[293] 2 doses
2 weeks[294]
2–8 °C[294] Phase III (32,000)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
May 2021 – ?, Russia[295]
Full (0)
Emergency (1)
QazCovid-in (QazVac)[296]
Research Institute for Biological Safety Problems
Kazakhstan Inactivated SARS‑CoV‑2 2 doses
3 weeks[297]
2–8 °C[298] Phase III (3,000)
Randomised, blind, placebo-controlled trial[299]
Mar 2021 – Jul 2021, Kazakhstan[299]
Full (0)
Emergency (1)
Sputnik Light
Gamaleya Research Institute of Epidemiology and Microbiology[300]
Russia Adenovirus vector (recombinant Ad26)[301] 1 dose[301] 2–8 °C[302] Phase III (7,000)[303]
Randomised, double-blind, placebo-controlled trial[301]
Feb  – Dec 2021, Russia
Full (0)
Emergency (1)

Vaccine candidates in human trials

COVID‑19 candidate vaccines in Phase I–III trials[3][304][305]
Vaccine candidates,
developers, and sponsors
Country of origin Type (technology) Current phase (participants)
design
Completed phase[f] (participants)
Immune response
Pending authorization
Novavax COVID-19 vaccine (Covovax)[126][306]
Novavax, CEPI
United States Subunit[307][308][309]/virus-like particle[310][311] (SARS‑CoV‑2 recombinant spike protein nanoparticle with adjuvant) Phase III (45,000)
Randomised, observer-blinded, placebo-controlled trial[312]
Sep 2020 – Jan 2021, UK (15,000); December 2020 – Mar 2021, US, Mexico, (30,000);[313] India[314]
Phase I–II (131)
IgG and neutralizing antibody response with adjuvant after booster dose.[315]
Emergency (8)
Sanofi–GSK COVID-19 vaccine (VAT00002)
Sanofi Pasteur, GSK
France, United Kingdom Subunit Phase III (34,520)[325]
Efficacy, Immunogenicity, and Safety of SARS-CoV-2 Recombinant Protein Vaccine with Adjuvant in Adults 18 Years of Age and Older.
Dec 2020 – Apr 2022, Kenya, United States
Phase I–II (1,160)
Phase I-IIa (440): Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine Formulations (With or Without Adjuvant) in Healthy Adults 18 Years of Age and Older.[326]
Phase IIb (720): Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine With AS03 Adjuvant in Adults 18 Years of Age and Older.[327]
Sep 2020 – Apr 2022, United States
Emergency (4)
CureVac COVID-19 vaccine (CVnCoV)
CureVac, CEPI
Germany RNA (unmodified RNA)[332] Phase III (40,400)[333][334][335][336]
Phase 2b/3 (36,500): Multicenter efficacy and safety trial in adults.
Phase 3 (2,520): Randomized, observer-blinded, placebo-controlled.
Phase 3 (180+1,200): Open-label.
Nov 2020 – Sep 2021, Argentina, Belgium, Colombia, Dominican Republic, France, Germany, Mexico, Netherlands, Panama, Peru, Spain
Phase I–II (944)[337][338]
Phase I (284): Partially blind, controlled, dose-escalation to evaluate safety, reactogenicity and immunogenicity.
Phase IIa (660):Partially observer-blind, multicenter, controlled, dose-confirmation.
Jun 2020 – Oct 2021, Belgium (phase I), Germany (phase I), Panama (phase IIa), Peru (phase IIa)
Emergency (2)
CoVLP[340][341]
Medicago, GSK
Canada, United Kingdom Virus-like particles[g] (recombinant, plant-based with AS03) Phase III (30,918)
Event-driven, randomized, observer blinded, placebo-controlled[343]
Nov 2020 – Dec 2021, Canada
Phase I (180)
Neutralizing antibodies at day 42 after the first injection (day 21 after the second injection) were at levels 10x that of COVID-19 survivors.
Jul 2020 – Sept 2021, Canada[344]
Emergency (1)
SOBERANA 02 (FINLAY-FR-2)
Instituto Finlay de Vacunas
Cuba Subunit (conjugate) Phase III (44,010)[346][347]
Multicenter, adaptive, parallel-group, randomized, placebo-controlled, double-blind
Mar–May 2021, Cuba, Iran, Venezuela[348]
Phase I–II (950)[349][350]
Phase I (40): Non-randomized controlled trial. Masking: Open. Control group: Uncontrolled. Study design: Adaptive, sequential
Phase II (910): Randomized controlled trial. Masking: Double Blind. Control group: Placebo. Study design: Parallel.
Nov 2020 – Mar 2021, Cuba
Emergency (1)
VLA2001[122][123]
Valneva
France Inactivated SARS‑CoV‑2 Phase III (4,000)[352][353]
Randomized, observer-blind, controlled.
Apr–Jul 2021, United Kingdom
Phase I–II (150)
Randomized, multi-center, double-blinded
Dec 2020 – Feb 2021, United Kingdom
Emergency (1)
COVIran Barakat[355]
Barakat Pharmaceutical Group, Shifa Pharmed Industrial Group
Iran Inactivated SARS‑CoV‑2 Phase III (52,000)
Phase II-IIIa (20,000): Randomized, double-blind, parallel arms, placebo-controlled.[356]
Phase IIIb (32,000)[357]
Mar–Jun 2021, Iran
Phase I (56)
Randomized, double-blind, parallel arms, placebo-control.[358]
Dec 2020 – Feb 2021, Iran
CIGB-66 (ABDALA)
Center for Genetic Engineering and Biotechnology
Cuba Subunit Phase III (48,000)[359]
Multicenter, randomized, double-blind, placebo-controlled.
Mar–Jul 2021, Cuba
Phase I–II (132)[360]
Randomized, double-blind, placebo-controlled, factorial.
Nov 2020 – May 2021, Cuba
Chinese Academy of Medical Sciences COVID-19 vaccine[361][362]
Chinese Academy of Medical Sciences
China Inactivated SARS‑CoV‑2 Phase III (34,020)
Randomized, double-blinded, single-center, placebo-controlled
Jan–Sep 2021, Brazil, Malaysia
Phase I–II (942)
Randomized, double-blinded, single-center, placebo-controlled
May–Sep 2020, Chengdu
ZyCoV-D[129]
Cadila Healthcare,
Biotechnology Industry Research Assistance Council
India DNA (plasmid expressing SARS‑CoV‑2 S protein) Phase III (28,216)[363][364]
Randomised, blind, placebo-controlled trial[365]
Jan–May 2021, India[366]
Phase I–II (1,000)
Interventional; randomized, double-blind, placebo-controlled[367][365]
Jul 2020 – Jan 2021, India
Walvax COVID-19 vaccine (ARCoV)[368]
PLA Academy of Military Science, Walvax Biotech,[369] Suzhou Abogen Biosciences
China RNA Phase III (28,000)
Multi-center, Randomized, Double-blind, Placebo-controlled
May–Oct 2021, China[370]
Phase I–II (588)
Phase I (168)
Phase II (420)
Jun 2020 – Mar 2022, China[371]
Minhai COVID-19 vaccine
Minhai Biotechnology Co., Shenzhen Kangtai Biological Products Co. Ltd.
China Inactivated SARS‑CoV‑2 (vero cell) Phase III (28,000)[372]
Multi-national, Randomized, Double-blind, Placebo-controlled.
May–Nov 2021, China
Phase I–II (1,180)[373][374]
Randomized, double-blind, placebo parallel-controlled.
Oct 2020 – Jun 2021, China
Nanocovax[375]
Nanogen Pharmaceutical Biotechnology JSC
Vietnam Subunit (SARS‑CoV‑2 recombinant spike protein with aluminum adjuvant)[376][377] Phase III (15,000)[378]
May–Sep 2021, Vietnam
Phase I–II (620)[379]
Phase I (60): Open label, dose escalation.
Phase II (560): Randomization, double-blind, multicenter, placebo-controlled.
Dec 2020 – Jun 2021, Vietnam
Bio E COVID-19 (BECOV2D)[380][381]
Biological E. Limited, Baylor College of Medicine,[382] CEPI
India, United States Subunit (using an antigen) Phase III (1,268)[383]
Apr 2021 – ?, India
Phase I–II (360)[384]
Randomized, Parallel Group Trial
Nov 2020 – Feb 2021, India
SCB-2019[385][386]
Clover Biopharmaceuticals,[387][388] CEPI
China Subunit (spike protein trimeric subunit with combined CpG 1018 and aluminium adjuvant) Phase II–III (22,000)
Randomized, double-blind, controlled
Mar 2021 – Jul 2022, Belgium, Brazil, Colombia, Dominican Republic, Germany, Nepal, Panama, the Philippines, Poland, South Africa
Phase I (150)
Jun–Oct 2020, Perth
UB-612
United Biomedical,Inc, COVAXX, DASA
Brazil, United States Subunit Phase II–III (11,170)[389][390]
Phase IIa (3,850): Placebo-controlled, Randomized, Observer-blind Study.
Phase IIb-III (7,320): Randomized, Multicenter, Double-Blind, Placebo Controlled, Dose-Response.
Jan 2021 – Mar 2023, Taiwan
Phase I (60)[391]
Open-label study
Sep 2020 – Jan 2021, Taiwan
GRAd-COV2[392][393]
ReiThera, Lazzaro Spallanzani National Institute for Infectious Diseases
Italy Adenovirus vector (modified gorilla adenovirus vector, GRAd) Phase II–III (10,300)[394][395]
Randomized, stratified, observer-blind, placebo-controlled.
Mar–May 2021, Italy
Phase I (90)[396]
Subjects (two groups: 18–55 and 65–85 years old) randomly receiving one of three escalating doses of GRAd-COV2 or a placebo, then monitored over a 24-week period. 93% of subjects who received GRAd-COV2 developed anti-bodies.
Aug–Dec 2020, Rome
West China Hospital COVID-19 vaccine
Jiangsu Province Centers for Disease Control and Prevention, West China Hospital
China Subunit (recombinant with Sf9 cell) Phase II (4,960)[397][398]
Phase IIa (960):Single-center, Randomized, Double-Blinded, Placebo-Controlled.
Phase IIb (4,000):Single-center, Randomized, Double-Blinded, Placebo-Controlled.
Nov 2020 – May 2021, China
Phase I (45)[399]
Single-center, Randomized, Placebo-controlled, Double-blind.
Aug–Oct 2020, China
MVC-COV1901
Medigen Vaccine Biologics
Taiwan Subunit Phase II (4,100)[400][401]
Phase IIa (3,700): Prospective, double-blinded, multi-center, multi-regional.
Phase IIb (400): Prospective, randomized, double-blind, dose-comparison, multi-center.
Dec 2020 – Sep 2021, Taiwan, Vietnam (phase IIa)
Phase I (45)[402]
Prospective, open-labeled, single-center
Oct 2020 – Jan 2021, Taiwan
V-01
Livzon Mabpharm, Inc.
China Subunit Phase II (880)[403]
Randomized, double-blind, and placebo-controlled.
Mar–May 2021, China
Phase I (180)[404]
Single-center, randomized, double-blind and placebo-controlled.
Feb–Mar 2021, China
DelNS1-2019-nCoV-RBD-OPT
Beijing Wantai Biological Pharmacy
China Viral vector Phase II (720)[405]
Nov 2020 – Dec 2021, China
Phase I (60)[406]
Sep 2020 – Oct 2021, China
Razi Cov Pars
Razi Vaccine and Serum Research Institute
Iran Subunit Phase II (500)[407]
Two parallel groups, randomized, double blind, placebo controlled.
Apr–Jun 2021, Iran
Phase I (133)[408]
Randomized, double blind, placebo controlled.
Jan–Mar 2021, Iran
Zhongyianke Biotech–Liaoning Maokangyuan Biotech COVID-19 vaccine
Zhongyianke Biotech, Liaoning Maokangyuan Biotech, Academy of Military Medical Sciences
China Subunit (Recombinant) Phase II (480)[409]
Single-center, randomized, double blinded, placebo controlled.
Mar–Jul 2021, China
Phase I (216)[410]
Randomized, placebo-controlled, double-blind.
Oct 2020 – Apr 2021, China
ERUCOV-VAC
Health Institutes of Turkey
Turkey Inactivated SARS‑CoV‑2 Phase II (250)[411]
Phase 2 Study for the Determination of Efficacy, Immunogenicity and Safety of Two Different Strengths of the Inactivated COVID-19 Vaccine ERUCOV-VAC, in a Placebo Controlled, Randomized, Double Blind Study Design.
Feb–Apr 2021, Turkey
Phase I (44)[412]
Study for the Determination of Safety and Immunogenicity of Two Different Strengths of the Inactivated COVID-19 Vaccine ERUCOV-VAC, Given Twice Intramuscularly to Healthy Volunteers, in a Placebo Controlled Study Design.
Nov 2020 – Mar 2021, Turkey
INO-4800[130][131]
Inovio, CEPI, Korea National Institute of Health, International Vaccine Institute
South Korea, United States DNA vaccine (plasmid delivered by electroporation) Phase II–III (7,218)
Phase II/III (6,578): Randomized, placebo-controlled, multi-center.[413]
Phase IIa (640): Randomized, double-blinded, placebo-controlled, dose-finding.[414]
Nov 2020 – Sep 2022, United States (phase II/III)[h] China (phase IIa)
Phase I–II (280)
Phase Ia (120): Open-label trial.
Phase Ib-IIa (160): Dose-Ranging Trial.[415]
April 2020 – Feb 2022, United States, South Korea (phase Ib-IIa)
AG0302-COVID‑19[132][416]
AnGes Inc.,[417] AMED
Japan DNA vaccine (plasmid) Phase II–III (500)
Randomized, double-blind, placebo controlled[418]
Nov 2020 – Apr 2021, Japan
Phase I–II (30)
Randomized/non-randomized, single-center, two doses
Jun–Nov 2020, Osaka
Unnamed
National Vaccine and Serum Institute, Lanzhou Institute of Biological Products Co., Ltd., Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd., Zhengzhou University
China Subunit (Recombinant) Phase I–II (3,580)[419]
Phase I/II Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of Recombinant SARS-CoV-2 Vaccine (CHO Cell) in Healthy People Aged 3 Years and Older.
Apr 2021 – Oct 2022, China
Preclinical
IIBR-100 (Brilife)[137]
The Israel Institute for Biological Research
Israel Vesicular stomatitis vector (recombinant) Phase I–II (1,040)[420]
Oct 2020 – May 2021, Israel
Preclinical
Arcturus COVID-19 vaccine (ARCT-021)[421][422]
Arcturus Therapeutics, Duke–NUS Medical School
United States, Singapore RNA Phase I–II (798)
Phase I/II (92): Randomized, double-blinded, placebo controlled
Phase IIa (106): Open label extension[423]
Phase IIb (600): Randomized, observer-blind, placebo-controlled[424]
Aug 2020 – Apr 2022, Singapore, United States (phase IIb)
Preclinical
VBI-2902[425]
Variation Biotechnologies
United States Virus-like particle Phase I–II (780)[426]
Randomized, observer-blind, dose-escalation, placebo-controlled
Mar 2021 – Jun 2022, Canada
Preclinical
NDV-HXP-S
Mahidol University, University of Texas at Austin
Thailand, United States Viral vector Phase I–II (460)[427]
Randomized, placebo-controlled, observer-blind.
Mar 2021 – Apr 2022; Brazil, Mexico, Thailand, Vietnam[428]
Preclinical
Sanofi–Translate Bio COVID-19 vaccine (MRT5500)[429]
Sanofi Pasteur and Translate Bio
France, United States RNA Phase I–II (415)[430]
Immunogenicity and Safety of the First-in-Human SARS-CoV-2 mRNA Vaccine Formulation in Healthy Adults 18 Years of Age and Older.
Mar 2021 – May 2022, United States
Preclinical
COVIVAC[431]
Institute of Vaccines and Medical Biologicals
Vietnam Viral vector/Egg-based, inactivated, whole chimeric Newcastle Disease Virus (NDV) expressing membrane-anchored pre-fusion-stabilized trimeric SARS-CoV-2 S protein (Hexapro) + CpG 1018.[432] Phase I–II (420)[433][434]
Phase I-II (120-300):Randomized, placebo-controlled, observer-blind.
Mar 2021 – May 2022, Vietnam
Preclinical
EuCorVac-19[435]
EuBiologics Co
South Korea Subunit Phase I–II (280)
Dose-exploration, randomized, observer-blind, placebo-controlled
Feb 2021 – Mar 2022, South Korea
Preclinical
RBD SARS-CoV-2 HBsAg VLP
SpyBiotech
United Kingdom Virus-like particle Phase I–II (280)[436]
Randomized, placebo-controlled, multi-center.
Aug 2020 – ?, Australia
Preclinical
GX-19 (GX-19N)[133][437][134]
Genexine consortium,[438] International Vaccine Institute
South Korea DNA vaccine Phase I–II (380)
Phase I-II (170-210): Multi-center, randomized, double-blind, placebo-controlled
Jun 2020 – Mar 2021, Seoul
Preclinical
AV-COVID-19
AIVITA Biomedical, Inc., Ministry of Health (Indonesia)
United States, Indonesia Viral vector Phase I–II (202)[439][440]
Adaptive.
Dec 2020 – Jul 2021, Indonesia (phase I), United States (phase I/II)
Preclinical
TAK-919[441]
Takeda
Japan RNA Phase I–II (200)[442]
Randomized, observer-blind, placebo-controlled
Jan 2021 – Mar 2022, Japan
Preclinical
TAK-019[443]
Takeda
Japan Subunit Phase I–II (200)[444]
Randomized, observer-blind, placebo-controlled.
Feb 2021 – April 2022, Japan
Preclinical
COVID-eVax
Takis Biotech
Italy DNA Phase I–II (160)[445]
Phase I:First-in-human, dose escalation.
Phase II: Open-label, randomize, dose expansion.
Feb–Sep 2021, Italy
Preclinical
ChulaCov19
Chulalongkorn University
Thailand RNA Phase I–II (96)[446]
Dose-finding Study.
Jan–Mar 2021, Thailand
Preclinical
COVID‑19/aAPC[135]
Shenzhen Genoimmune Medical Institute[447]
China Lentiviral vector (with minigene modifying aAPCs) Phase I (100)
Mar 2020 – Jul 2023, Shenzhen
Preclinical
LV-SMENP-DC[136]
Shenzhen Genoimmune Medical Institute[447]
China Lentiviral vector (with minigene modifying DCs) Phase I (100)
Mar 2020 – Jul 2023, Shenzhen
Preclinical
ImmunityBio COVID-19 vaccine (hAd5)
ImmunityBio
United States Viral vector Phase I–II (540)[448][449][450][451][452]
Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of a Subcutaneously- and Orally- Administered Supplemental Spike & Nucleocapsid-targeted COVID-19 Vaccine to Enhance T Cell Based Immunogenicity in Participants Who Have Already Received Prime + Boost Vaccines Authorized For Emergency Use.
Oct 2020  – Sep 2021, South Africa, United States
Preclinical
COVAX-19[453]
Vaxine Pty Ltd[454]
Australia Subunit (recombinant protein) Phase I (40)
Jun 2020 – Jul 2021, Adelaide
Preclinical
HGC019[455]
Gennova Biopharmaceuticals, HDT Biotech Corporation[456]
India, United States RNA Phase I (120)[457]
Jan 2021 – ?, India
Preclinical
Bangavax (Bancovid)[458][459]
Globe Biotech Ltd. of Bangladesh
Bangladesh RNA Awaiting for approval from Bangladesh government to conduct the first clinical trial.[460] Preclinical
PTX-COVID19-B[461]
Providence Therapeutics
Canada RNA Phase I (60)[461]
First-in-Human, Observer-Blinded, Randomized, Placebo Controlled.[462]
Jan–May 2021, Canada
Preclinical
COVAC-2[463]
VIDO (University of Saskatchewan)
Canada Subunit Phase I (108)[463]
Randomized, observer-blind, dose-escalation.[464]
Feb 2021 – Oct 2022, Halifax
Preclinical
COVI-VAC
Codagenix Inc.
United States Attenuated Phase I (48)[465]
First-in-human, randomised, double-blind, placebo-controlled, dose-escalation
Dec 2020 – Jun 2021, United Kingdom
Preclinical
CoV2 SAM (LNP)
GSK
United Kingdom RNA Phase I (40)[466]
Open-label, dose escalation, non-randomized
Feb–Jun 2021, United States
Preclinical
COVIGEN
University of Sydney
Australia DNA Phase I (150)[467]
Double-blind, dose-ranging, randomised, placebo-controlled.
Feb 2021 – Jun 2022, Sydney
Preclinical
BBV154[468]
Bharat Biotech[469]
India Adenovirus vector (intranasal) Phase I (175)[468]
Randomized, double-blinded, multicenter.
Mar 2021, India
Preclinical
MV-014-212[470]
Meissa Vaccine Inc.
United States Attenuated Phase I (130)[471]
Randomized, double-blinded, multicenter.
Mar 2021 – Oct 2022, United States
Preclinical
S-268019
Shionogi
Japan Subunit Phase I–II (214)[472]
Randomized, double-blind, placebo-controlled, parallel-group.
Dec 2020 – Jun 2022, Japan
Preclinical
GBP510
SK Bioscience Co. Ltd.
South Korea Subunit Phase I–II (580)[473][474]
Phase I-II (260-320): Placebo-controlled, randomized, observer-blinded, dose-finding.
Jan–Aug 2021, South Korea
Preclinical
KBP-201
Kentucky Bioprocessing
United States Subunit Phase I–II (180)[475]
First-in-human, observer-blinded, randomized, placebo-controlled, parallel group
Dec 2020 – May 2021, United States
Preclinical
AdCLD-CoV19
Cellid Co
South Korea Viral vector Phase I–II (150)[476]
Phase I: Dose Escalation, Single Center, Open.
Phase IIa: Multicenter, Randomized, Open.
Dec 2020 – Mar 2021, South Korea
Preclinical
AdimrSC-2f
Adimmune Corporation
Taiwan Subunit Phase I (70)[477]
Randomized, single center, open-label, dose-finding.
Aug–Nov 2020, Taiwan
Preclinical
AKS-452
University Medical Center Groningen
Netherlands Subunit Phase I–II (130)[478]
Non-randomized, Single-center, open-label, combinatorial.
Apr–Jun 2021, Netherlands
Preclinical
GLS-5310
GeneOne Life Science Inc.
South Korea DNA Phase I–II (345)[479]
Multicenter, Randomized, Combined Phase I Dose-escalation and Phase IIa Double-blind.
Dec 2020 – Jul 2022, South Korea
Preclinical
Covigenix VAX-001
Entos Pharmaceuticals Inc.
Canada DNA Phase I–II (72)[480]
Placebo-controlled, randomized, observer-blind, dose ranging adaptive.
Mar–Aug 2021, Canada
Preclinical
COH04S1
City of Hope Medical Center
United States Viral vector Phase I (129)[481]
Dose Escalation Study.
Dec 2020 – Nov 2022, California
Preclinical
FAKHRAVAC (MIVAC)
Organization of Defensive Innovation and Research
Iran Inactivated SARS‑CoV‑2 Phase I (135)[482]
Randomized, double blind, controlled trial with factorial design.
Mar–Apr 2021, Iran
Preclinical
NBP2001
SK Bioscience Co. Ltd.
South Korea DNA Phase I (50)[483]
Placebo-controlled, Randomized, Observer-blinded, Dose-escalation.
Dec 2020 – Apr 2021, South Korea
Preclinical
CoVac-1
University of Tübingen
Germany Subunit Phase I (36)[484]
Placebo-controlled, Randomized, Observer-blinded, Dose-escalation.
Nov 2020 – Sep 2021, Germany
Preclinical
bacTRL-Spike
Symvivo
Canada DNA Phase I (24)[485]
Randomized, observer-blind, placebo-controlled.
Nov 2020 – Feb 2022, Australia
Preclinical
CORVax12
Providence Health & Services
United States DNA Phase I (36)[486]
Open-label.
Dec 2020 – May 2021, United States
Preclinical
ChAdV68-S (SAM-LNP-S)
NIAID, Gritstone Oncology
United States Viral vector Phase I (130)[487]
Open-label, dose and age escalation, parallel design.
Mar 2021 – Sep 2022, United States
Preclinical
AdCOVID
Altimmune Inc.
United States Viral vector Phase I (180)[488]
Double-blind, randomized, placebo-controlled, first-in-Human.
Feb 2021 – Feb 2022, United States
Preclinical
VXA-CoV2-1
Vaxart
United States Viral vector Phase I (35)[489]
Double-blind, randomized, placebo-controlled, first-in-Human.
Sep 2020 – May 2021, United States
Preclinical
SpFN COVID-19 vaccine
United States Army Medical Research and Development Command
United States Subunit Phase I (72)[490]
Randomized, double-blind, placebo-controlled.
Apr 2021 – Oct 2022, United States
Preclinical
MVA-SARS-2-S
University Medical Center Hamburg-Eppendorf
Germany Viral vector Phase I (30)[491]
Open, Single-center.
Oct 2020 – May 2021, Germany
Preclinical
ReCOV
Jiangsu Rec-Biotechnology Co Ltd
China Subunit Phase I (160)[492]
First-in-human, randomized, double-blind, placebo-controlled, dose-finding.
Apr–Jul 2021, New Zealand
Preclinical
DelNS1-nCoV-RBD LAIV
University of Hong Kong
Hong Kong Attenuated Phase I (115)[493]
Randomized, double-blinded, placebo-controlled, dose-escalation, and dose-expansion.
Mar 2021 – Sep 2022, Hong Kong
Preclinical
SARS-CoV-2 VLP vaccine
Ihsan Gursel, Scientific and Technological Research Council of Turkey
Turkey Virus-like particle Phase I (36)[494]
double-blinded, randomised, placebo controlled.
Mar 2021 – Jan 2022, Turkey
Preclinical
Koçak-19 Inaktif Adjuvanlı COVID-19 vaccine
Kocak Farma
Turkey Inactivated SARS‑CoV‑2 Phase I (38)[495]
Phase 1 Study for the Determination of Safety and Immunogenicity of Different Strengths of Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine, Given Twice Intramuscularly to Healthy Volunteers, in a Placebo Controlled Study Design.
Mar–Jun 2021, Turkey
Preclinical
mRNA-1283
Moderna
United States RNA Phase I (125)[496]
Randomized, observer-blind, dose-ranging study.
Mar 2021 – Apr 2022, United States
Preclinical
DS-5670[497]
Daiichi Sankyo[498]
Japan RNA Phase I–II (152)[499]
A Phase 1/2 Study to Assess the Safety, Immunogenicity and Recommended Dose of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects.
Mar 2021 – Jul 2022, Japan
Preclinical
Adenovirus Type-5 Vectored COVID-19 vaccine
Jiangsu Province Centers for Disease Control and Prevention
China Viral vector Phase I (89)[500]
Single-center, open-label.
Sep–Oct 2020, China
Preclinical
KD-414
KM Biologics Co
Japan Inactivated SARS‑CoV‑2 Phase I–II (210)[501]
Randomized, double blind, placebo control, parallel group.[502]
Mar 2021 – Dec 2022, Japan
Preclinical
CoVepiT
OSE Immunotherapeutics
France Subunit Phase I (48)[503]
Apr 2021 – ?, France
Preclinical
ABNCoV2
Bavarian Nordic.[504] Radboud University Nijmegen
Denmark, Netherlands Virus-like particle Phase I (42)[505]
Single center, sequential dose-escalation, open labelled trial.
Mar–Dec 2021, Netherlands
Preclinical
HDT-301
Senai Cimatec
Brazil RNA Phase I (78)[506]
Randomized, open-label, dose-escalation.
May–Sep 2021, Brazil
Preclinical
SC-Ad6-1
Tetherex Pharmaceuticals
United States Viral vector Phase I (40)[507]
First-In-Human, Open-label, Single Ascending Dose and Multidose.
Jun–Dec 2021, Australia
Preclinical
Unnamed
Osman ERGANIS, Scientific and Technological Research Council of Turkey
Turkey Inactivated SARS‑CoV‑2 Phase I (50)[508]
Phase I Study Evaluating the Safety and Efficacy of the Protective Adjuvanted Inactivated Vaccine Developed Against SARS-CoV-2 in Healthy Participants, Administered as Two Injections Subcutaneously in Two Different Dosages.
Apr–Oct 2021, Turkey
Preclinical
EXG-5003
Elixirgen Therapeutics, Fujita Health University
Japan, United States RNA Phase I–II (60)[509]
First in Human, randomized, placebo-controlled.
Apr 2021 – Jan 2023, Japan
Preclinical
Patria[510]
Laboratorio Avimex, National Council of Science and Technology
Mexico Viral vector Phase I (90)[511]
Dose-escalation, open-label, non-randomized.
Apr–Aug 2021, Mexico
Preclinical
Unnamed
Sinopharm
China Subunit Phase I–II (?)[512]
Apr 2021, China
Preclinical
Unnamed
North's Academy of Medical Science Medical biology institute
North Korea Subunit (spike protein with Angiotensin-converting enzyme 2) Phase I–II (?)[513]
Jul 2020, North Korea
Preclinical
LNP-nCoVsaRNA[514]
MRC clinical trials unit at Imperial College London
United Kingdom RNA Terminated (105)
Randomized trial, with dose escalation study (15) and expanded safety study (at least 200)
Jun 2020 – Jul 2021, United Kingdom
?
TMV-083
Institut Pasteur
France Viral vector Terminated (90)[515]
Randomized, Placebo-controlled.
Aug 2020 – Jun 2021, Belgium, France
?
SARS-CoV-2 Sclamp/V451[127][128]
UQ, Syneos Health, CEPI, Seqirus
Australia Subunit (molecular clamp stabilized spike protein with MF59) Terminated (120)
Randomised, double-blind, placebo-controlled, dose-ranging.
False positive HIV test found among participants.
Jul–Oct 2020, Brisbane
?
V590[516] and V591/MV-SARS-CoV-2[517] Merck & Co. (Themis BIOscience), Institut Pasteur, University of Pittsburgh's Center for Vaccine Research (CVR), CEPI United States, France Vesicular stomatitis virus vector[518] / Measles virus vector[519] Terminated
In phase I, immune responses were inferior to those seen following natural infection and those reported for other SARS-CoV-2/COVID-19 vaccines.[520]
  1. ^ Serum Institute of India will be producing the ChAdOx1 nCoV-19 vaccine for India[214] and other low- and middle-income countries.[215]
  2. ^ Oxford name: ChAdOx1 nCoV-19. Manufacturing in Brazil to be carried out by Oswaldo Cruz Foundation.[216]
  3. ^ a b Recommended interval. The second dose of the Pfizer–BioNTech and Moderna vaccines can be administered up to six weeks after the first dose to alleviate a shortage of supplies.[223][224]
  4. ^ Long-term storage temperature. The Pfizer–BioNTech COVID-19 vaccine can be kept between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use, and between 2 and 8 °C (36 and 46 °F) for up to five days before use.[225][226]
  5. ^ Storage temperature for the frozen Gam-COVID-Vac formulation. The lyophilised Gam-COVID-Vac-Lyo formulation can be stored at 2-8°C.[233]
  6. ^ Latest Phase with published results.
  7. ^ Virus-like particles grown in Nicotiana benthamiana[342]
  8. ^ Phase I–IIa in South Korea in parallel with Phase II–III in the US

Formulation

As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity.[27] An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen, such as the COVID‑19 virus or influenza virus.[521] Specifically, an adjuvant may be used in formulating a COVID‑19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID‑19 infection in vaccinated individuals.[521][522] Adjuvants used in COVID‑19 vaccine formulation may be particularly effective for technologies using the inactivated COVID‑19 virus and recombinant protein-based or vector-based vaccines.[522] Aluminum salts, known as "alum", were the first adjuvant used for licensed vaccines, and are the adjuvant of choice in some 80% of adjuvanted vaccines.[522] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines.[521][522]

Distribution

Location Vaccinated[b] % of pop.[c]
  World[d] 655,467,201 8.4%
 China[e] 332,964,000 --
 United States 152,819,904 45.7%
 EU 126,088,333 28.3%
 India 135,192,013 9.8%
 United Kingdom 35,472,295 52.2%
 Brazil 32,101,075 15.1%
 Germany 27,306,096 32.6%
 France 17,829,181 26.2%
 Turkey 14,618,167 17.3%
 Italy 17,119,653 28.3%
 Indonesia 13,349,469 4.9%
 Russia 13,165,465 9.0%
 Mexico 14,148,207 11.0%
 Spain 13,797,431 29.5%
 Canada 14,991,030 39.7%
 Chile 8,561,191 44.8%
 Poland 10,260,941 27.1%
 United Arab Emirates[e] 11,186,348 --
 Saudi Arabia[e] 10,751,126 --
 Israel 5,424,961 62.7%
 Morocco 5,726,928 15.5%
 Bangladesh 5,819,900 3.5%
 Argentina 7,718,272 17.1%
 Hungary 4,346,089 45.0%
 Colombia 3,861,416 7.6%
 Romania 3,629,484 18.9%
 Netherlands 4,448,730 26.0%
 Japan 3,500,968 2.8%
 Belgium 3,560,768 30.7%
 South Korea 3,692,566 7.2%
 Portugal 2,895,611 28.4%
 Serbia 2,149,705 31.6%
 Greece 2,507,229 24.1%
 Czech Republic 2,682,293 25.1%
 Sweden 2,852,689 28.2%
 Austria 2,665,516 29.6%
 Pakistan[e] 3,320,304 --
 Switzerland 1,997,717 23.1%
 Cambodia 1,825,488 10.9%
 Australia[e] 2,663,221 --
 Nepal 2,091,511 7.2%
 Philippines 1,957,511 1.8%
 Denmark 1,505,134 26.0%
 Dominican Republic 1,543,725 14.2%
 Mongolia 1,643,030 50.1%
 Singapore 1,364,124 23.3%
 Kazakhstan 1,634,939 8.7%
 Finland 1,944,725 35.1%
 Peru 1,387,718 4.2%
 Uruguay 1,236,574 35.6%
 Norway 1,485,659 27.4%
 Qatar 1,127,091 39.1%
 Ireland 1,347,561 27.5%
 Slovakia 1,227,189 22.5%
 Thailand 1,296,440 1.9%
 Hong Kong 1,087,202 14.5%
 Malaysia 1,089,637 3.4%
 Azerbaijan 1,005,704 9.9%
 Nigeria 1,665,698 0.8%
 Iran 1,231,652 1.5%
 Kuwait[e] 1,440,000 --
 Bahrain 806,143 47.4%
 Ecuador 981,620 5.6%
 Ethiopia[e] 1,215,934 --
 Lithuania 792,671 29.1%
 Croatia 879,312 21.4%
 Sri Lanka 931,276 4.3%
 El Salvador 958,828 14.8%
 Jordan 805,020 7.9%
 Myanmar 1,000,000 1.8%
 Bulgaria 651,694 9.4%
 Costa Rica 605,099 11.9%
 Bolivia 637,694 5.5%
 Ukraine 865,588 2.0%
 Kenya 853,081 1.6%
 Vietnam 851,513 0.9%
 Ghana 849,527 2.7%
 Panama 524,958 12.2%
 Slovenia 486,290 23.4%
 Zimbabwe 526,066 3.5%
 Egypt 660,000 0.6%
 Uzbekistan 600,369 1.8%
 Albania[e] 596,766 --
 Estonia 373,391 28.1%
 Lebanon 325,383 4.8%
 Tunisia 350,426 3.0%
 Bhutan 481,491 62.4%
 Angola 456,349 1.4%
 Maldives 300,906 55.7%
 Senegal 427,377 2.5%
 Latvia 323,779 17.2%
 Uganda 395,805 0.9%
 South Africa 395,230 0.7%
 Malta 246,698 55.9%
 Rwanda 350,400 2.7%
 Cyprus 252,792 28.9%
 Belarus 244,000 2.6%
 Oman 253,000 5.0%
 Malawi 319,323 1.7%
 New Zealand 217,603 4.5%
 Iraq 298,377 0.7%
 Ivory Coast 262,639 1.0%
 Venezuela 250,000 0.9%
 Luxembourg 175,126 28.0%
 Afghanistan 240,000 0.6%
 Palestine 170,109 3.3%
 Guatemala 204,459 1.1%
 Moldova 161,849 4.0%
 Laos 126,072 1.7%
 Iceland 138,577 40.6%
 Guinea 116,436 0.9%
 Togo 160,000 1.9%
 Guyana 150,694 19.2%
 Paraguay 131,013 1.8%
 Sudan 140,227 0.3%
 Jamaica 135,473 4.6%
 Nicaragua 135,130 2.0%
 Seychelles 68,045 69.2%
 Northern Cyprus 71,737 18.8%
 North Macedonia 121,181 5.8%
 Macau 78,460 12.1%
 Somalia 117,567 0.7%
 Mauritius 117,323 9.2%
 Montenegro 83,498 13.3%
 Curaçao 77,334 47.1%
 Bosnia and Herzegovina 83,260 2.5%
 Taiwan[e] 92,049 --
 Jersey 53,044 52.5%
 Aruba 56,009 52.5%
 Zambia 81,459 0.4%
 Isle of Man 59,932 70.5%
 Equatorial Guinea 64,646 4.6%
 Barbados 75,476 26.3%
 Algeria[e] 75,000 --
 Gibraltar 38,727 115.0%
 Cayman Islands 37,470 57.0%
 Sierra Leone 58,250 0.7%
 Trinidad and Tobago 60,245 4.3%
 Georgia 58,533 1.5%
 Bermuda 32,877 52.8%
 Honduras 55,000 0.6%
 Mozambique 57,305 0.2%
 Fiji 56,000 6.2%
 Mali 49,903 0.2%
 Botswana 49,882 2.1%
 Belize 47,675 12.0%
 Guernsey 32,969 49.2%
 Suriname 44,918 7.7%
 Namibia 34,346 1.4%
 Eswatini 34,897 3.0%
 San Marino 21,389 63.0%
 Dominica 18,864 26.2%
 Antigua and Barbuda 29,754 30.4%
 Andorra 24,182 31.3%
 Kyrgyzstan 27,000 0.4%
 Bahamas 25,692 6.5%
 Saint Lucia[e] 25,248 --
 Turks and Caicos Islands 15,039 38.8%
 Monaco 12,758 32.5%
 Faroe Islands 16,896 34.6%
 Kosovo 22,096 1.1%
 Gambia 20,922 0.9%
 Grenada 13,000 11.6%
 Lesotho 16,000 0.8%
 Greenland 9,326 16.4%
 Saint Vincent and the Grenadines[e] 14,526 --
 Congo 14,297 0.3%
 Liechtenstein 9,645 25.3%
 Comoros 13,440 1.6%
 Saint Kitts and Nevis 12,943 24.3%
 Cameroon 11,000 0.0%
 Brunei 10,715 2.5%
 Djibouti 10,246 1.0%
 São Tomé and Príncipe 9,724 4.4%
 Gabon 6,895 0.3%
 Samoa[e] 7,435 --
 Mauritania 7,038 0.1%
 Anguilla 6,115 40.8%
 Tonga 5,367 5.1%
 Solomon Islands 4,890 0.7%
 Saint Helena 3,563 58.7%
 Falkland Islands 2,632 75.6%
 Papua New Guinea 2,900 0.0%
 East Timor 2,629 0.2%
 Syria 2,500 0.0%
 Cape Verde 2,184 0.4%
 Montserrat 1,293 25.9%
 DR Congo 1,700 0.0%
 Niger 1,366 0.0%
 South Sudan 947 0.0%
 Libya 750 0.0%
 Nauru 700 6.5%
 Armenia 565 0.0%
 F.S. Micronesia[524] 22,071 21.3%
 Marshall Islands[524] 15,490 26.5%
 Palau[524] 12,975 72.5%
 Vatican City[525][526] 22 2.7%

Sources

Notes

  1. ^ Latest available data as of this date. Individual country reporting frequency varies.
  2. ^ Number of unique individuals who have received at least one dose of a COVID-19 vaccine (unless noted otherwise).
  3. ^ Includes those who are partially vaccinated with a single dose. May include vaccination of non-citizen workers, which can push totals beyond 100% of the local population.
  4. ^ Some countries are not yet reporting first-dose counts. Total dose counts for these countries are not included in the World total.
  5. ^ a b c d e f g h i j k l m This country's data reflects total doses administered, not the first shot only.

As of 10 May 2021, 1.32 billion COVID-19 vaccine doses had been administered worldwide based on official reports from national health agencies collated by Our World in Data.[527]

During a pandemic on the rapid timeline and scale of COVID‑19 infections during 2020, international organizations like the WHO and CEPI, vaccine developers, governments, and industry are evaluating the distribution of the eventual vaccine(s).[528] Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country.[529][530][531][532] Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need.[529][530][532] In April 2020, it was reported that the UK agreed to work with 20 other countries and global organizations including France, Germany and Italy to find a vaccine and to share the results and that UK citizens would not get preferential access to any new COVID‑19 vaccines developed by taxpayer-funded UK universities.[533] Several companies plan to initially manufacture a vaccine at artificially low pricing, then increase prices for profitability later if annual vaccinations are needed and as countries build stock for future needs.[532]

An April 2020 CEPI report stated: "Strong international coordination and cooperation between vaccine developers, regulators, policymakers, funders, public health bodies, and governments will be needed to ensure that promising late-stage vaccine candidates can be manufactured in sufficient quantities and equitably supplied to all affected areas, particularly low-resource regions."[534] The WHO and CEPI are developing financial resources and guidelines for global deployment of several safe, effective COVID‑19 vaccines, recognizing the need is different across countries and population segments.[528][535][536][537] For example, successful COVID‑19 vaccines would likely be allocated first to healthcare personnel and populations at greatest risk of severe illness and death from COVID‑19 infection, such as the elderly or densely-populated impoverished people.[538][539]

The WHO, CEPI, and GAVI have expressed concerns that affluent countries should not receive priority access to the global supply of eventual COVID‑19 vaccines, but rather protecting healthcare personnel and people at high risk of infection are needed to address public health concerns and reduce economic impact of the pandemic.[534][536][538] WHO Director General Tedros Adhanom referred to subsequent inequities in the distribution as "a catastrophic moral failure".[540] A March 2021 survey of 77 epidemiologists concluded that mutations would render existing vaccines ineffective within one year — a window which wealthy nations were on pace to meet.[541] Conversely, an Economist Intelligence Unit report from earlier in the year estimated that a similar level of herd immunity would not be achieved globally until 2024.[540]

Inequity concerns

In a meeting in April 2021, the World Health Organization's emergency committee addressed concerns of persistent inequity in the global vaccine distribution.[542]

Liability

On 4 February 2020, US Secretary of Health and Human Services Alex Azar published a notice of declaration under the Public Readiness and Emergency Preparedness Act for medical countermeasures against COVID‑19, covering "any vaccine, used to treat, diagnose, cure, prevent, or mitigate COVID‑19, or the transmission of SARS-CoV-2 or a virus mutating therefrom", and stating that the declaration precludes "liability claims alleging negligence by a manufacturer in creating a vaccine, or negligence by a health care provider in prescribing the wrong dose, absent willful misconduct".[543] The declaration is effective in the United States through 1 October 2024.[543]

In December 2020, the UK government granted Pfizer legal indemnity for its COVID-19 vaccine.[544]

In the European Union, the COVID‑19 vaccines are licensed under a Conditional Marketing Authorisation which does not exempt manufacturers from civil and administrative liability claims.[545] While the purchasing contracts with vaccine manufacturers remain secret, they do not contain liability exemptions even for side-effects not known at the time of licensure.[546]

Pfizer has been criticised for demanding far-reaching liability waivers and other guarantees from countries such as Argentina and Brazil, which go beyond what was expected from other countries such as the US (above).[547][548]

Preventive measures after vaccination

While vaccines substantially reduce the probability of infection, is possible for fully vaccinated people to contract and spread COVID-19.[549] Public health agencies have recommended that vaccinated people continue using preventive measures (wear face masks, social distance, wash hands) to avoid infecting others, especially vulnerable people, particularly in areas with high community spead. Governments have indicated that such recommendations will be reduced as vaccination rates increase and community spread declines.[550]

Society and culture

Access

Nations pledged to buy doses of COVID‑19 vaccine before the doses were available. Though high-income nations represent only 14% of the global population, as of 15 November 2020, they had contracted to buy 51% of all pre-sold doses. Some high-income nations bought more doses than would be necessary to vaccinate their entire populations.[13]

Elderly receiving second dose of CoronaVac vaccine in Brazil.

On 18 January 2021, WHO Director-General Tedros Adhanom Ghebreyesus warned of problems with equitable distribution: "More than 39 million doses of vaccine have now been administered in at least 49 higher-income countries. Just 25 doses have been given in one lowest-income country. Not 25 million; not 25 thousand; just 25."[551]

Production of Sputnik V vaccine in Brazil

In March, it was revealed the US attempted to convince Brazil not to purchase the Sputnik V COVID-19 vaccine, fearing "Russian influence" in Latin America.[552] Some nations involved in long-standing territorial disputes have reportedly had their access to vaccines blocked by competing nations; Palestine has accused Israel blocking vaccine delivery to Gaza, while Taiwan has suggested that China has hampered its efforts to procure vaccine doses.[553][554][555]

A single dose of the COVID‑19 vaccine by AstraZeneca would cost 47 Egyptian pounds (EGP) and the authorities are selling it between 100 and 200 EGP. A report by Carnegie Endowment for International Peace cited the current poverty rate in Egypt as around 29.7 percent, which constitutes approximately 30.5 million people, and claimed that about 15 million of the Egyptians would be unable to gain access to the luxury of vaccination. A human rights lawyer, Khaled Ali launched a lawsuit against the government, forcing them to provide vaccination free of cost to all members of the public.[556]

According to immunologist Dr. Anthony Fauci, mutant strains of virus and limited vaccine distribution pose continuing risks and he said: "we have to get the entire world vaccinated, not just our own country."[557] Edward Bergmark and Arick Wierson are calling for an global vaccination effort and wrote that the wealthier nations' "me-first" mentality could ultimately backfire, because the spread of the virus in poorer countries would lead to more variants, against which current vaccines could be less effective.[558]

On 10 March 2021, the United States, Britain, European Union nations and other WTO members, blocked a push by more than eighty developing countries to waive COVID‑19 vaccine patent rights in an effort to boost production of vaccines for poor nations.[559] On 5 May 2021, the Biden administration announced that it supports waiving intellectual property protections for Covid-19 vaccines.[560]

Misinformation

Anti-vaccination activists and other people spread a variety of rumors, including overblown claims about side effects, a story about COVID-19 being spread by childhood vaccines, misrepresentations about how the immune system works, and when and how COVID-19 vaccines are made.

Vaccine hesitancy

Some 10% of the public perceives vaccines as unsafe or unnecessary, refusing vaccination – a global health threat called vaccine hesitancy[561] – which increases the risk of further viral spread that could lead to COVID‑19 outbreaks.[41] As of May 2020, estimates from two surveys were that 67% or 80% of people in the U.S. would accept a new vaccination against COVID‑19, with wide disparity by education level, employment status, ethnicity, and geography.[562] As of March 2021, 19% of US adults claim to have been vaccinated and 50% of US adults plan to get vaccinated.[563][564]

In an effort to demonstrate the vaccine's safety, prominent politicians have received it on camera, with others pledging to do so.[565][566][567]

Encouragement by public figures and celebrities

Many public figures and celebrities have publicly declared that they have been vaccinated against COVID‑19, and encouraged people to get vaccinated. Many have made video recordings or otherwise documented their vaccination. They do this partly to counteract vaccine hesitancy and COVID‑19 vaccine conspiracy theories.[568]

Politicians and heads of state

Peru's interim President Francisco Sagasti gets vaccinated against COVID-19 at a military hospital in Lima

Several current and former heads of state and government ministers have released photographs of their vaccinations, encouraging others to be vaccinated, including Kyriakos Mitsotakis, Zdravko Marić, Olivier Véran, Joe Biden, Barack Obama, George W. Bush, Bill Clinton, the Dalai Lama, Narendra Modi, Justin Trudeau, Alexandria Ocasio-Cortez, Nancy Pelosi and Kamala Harris.[569][570]

Elizabeth II and Prince Philip announced they had the vaccine, breaking from protocol of keeping the British royal family's health private.[568] Pope Francis and Pope Emeritus Benedict both announced they had been vaccinated.[568]

Musicians

Dolly Parton recorded herself getting vaccinated with the Moderna vaccine she helped fund, she encouraged people to get vaccinated and created a new version of her song "Jolene" called "Vaccine".[568] Patti Smith, Yo-Yo Ma, Carole King, Tony Bennett, Mavis Staples, Brian Wilson, Joel Grey, Loretta Lynn, Willie Nelson, and Paul Stanley have all released photographs of them being vaccinated and encouraged others to do so.[569] Grey stated "I got the vaccine because I want to be safe. We've lost so many people to COVID. I've lost a few friends. It's heartbreaking. Frightening."[569]

Actresses and actors

Amy Schumer, Rosario Dawson, Arsenio Hall, Danny Trejo, Mandy Patinkin, Samuel L. Jackson, Arnold Schwarzenegger, Sharon Stone, Kate Mulgrew, Jeff Goldblum, Jane Fonda, Anthony Hopkins, Bette Midler, Kim Cattrall, Isabella Rossellini, Christie Brinkley, Cameran Eubanks, Hugh Bonneville, Alan Alda, David Harbour, Sean Penn, Amanda Kloots, Ian McKellen and Patrick Stewart have released photographs of themselves getting vaccinated and encouraging others to do the same.[568][569] Dame Judi Dench and Joan Collins announced they have been vaccinated.[568]

TV personalities

Martha Stewart, Jonathan Van Ness, Al Roker and Dan Rather released photographs of themselves getting vaccinated and encouraged others to do the same.[568][569] Stephen Fry also shared a photograph of being vaccinated; he wrote, "It's a wonderful moment, but you feel that it's not only helpful for your own health, but you know that you're likely to be less contagious if you yourself happen to carry it ... It's a symbol of being part of society, part of the group that we all want to protect each other and get this thing over and done with."[568] Sir David Attenborough announced that he has been vaccinated.[568]

Athletes

Magic Johnson and Kareem Abdul-Jabbar released photographs of themselves getting vaccinated and encouraged others to do the same; Abdul-Jabbar said, "We have to find new ways to keep each other safe."[569]

Specific communities

Romesh Ranganathan, Meera Syal, Adil Ray, Sadiq Khan and others produced a video specifically encouraging ethnic minority communities in the UK to be vaccinated including addressing conspiracy theories stating "there is no scientific evidence to suggest it will work differently on people from ethnic minorities and that it does not include pork or any material of fetal or animal origin."[571]

Oprah Winfrey and Whoopi Goldberg have spoken about being vaccinated for COVID‑19 and encouraged black Americans to be vaccinated.[569] Stephanie Elam volunteered to be a trial volunteer stating "a large part of the reason why I wanted to volunteer for this COVID‑19 vaccine research – more Black people and more people of color need to be part of these trials so more diverse populations can reap the benefits of this medical research."[569]

See also

References

  1. ^ Li YD, Chi WY, Su JH, Ferrall L, Hung CF, Wu TC (December 2020). "Coronavirus vaccine development: from SARS and MERS to COVID-19". Journal of Biomedical Science. 27 (1): 104. doi:10.1186/s12929-020-00695-2. PMC 7749790. PMID 33341119.
  2. ^ Padilla T (24 February 2021). "No one is safe unless everyone is safe". BusinessWorld. Retrieved 24 February 2021.
  3. ^ a b c d e f "COVID-19 vaccine development pipeline (Refresh URL to update)". Vaccine Centre, London School of Hygiene and Tropical Medicine. 1 March 2021. Retrieved 10 March 2021.
  4. ^ Beaumont P (18 November 2020). "Covid-19 vaccine: who are countries prioritising for first doses?". The Guardian. ISSN 0261-3077. Retrieved 26 December 2020.
  5. ^ Plotkin SA, Halsey N (January 2021). "Accelerate COVID-19 Vaccine Rollout by Delaying the Second Dose of mRNA Vaccines". Clinical Infectious Diseases. doi:10.1093/cid/ciab068. PMC 7929065. PMID 33502467.
  6. ^ Epperly, David (January 2021). "Evidence For COVID-19 Vaccine Deferred Dose 2 Boost Timing". SSRN 3760833.
  7. ^ Wang X (February 2021). "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine". N Engl J Med (letter). 384 (11): 1576–78. doi:10.1056/NEJMc2036242. PMID 33596350.
  8. ^ "More Evidence: Evidence For COVID-19 Vaccine Deferred Dose 2 Boost Timing". ReallyCorrect.com.
  9. ^ "Coronavirus (COVID-19) Vaccinations – Statistics and Research". Our World in Data. Retrieved 7 February 2021.
  10. ^ "Which companies will likely produce the most COVID-19 vaccine in 2021?". Pharmaceutical Processing World. 5 February 2021. Retrieved 1 March 2021.
  11. ^ "China can hit 500-mln-dose annual capacity of CanSinoBIO COVID-19 vaccine this year". Yahoo! Sport. Retrieved 1 March 2021.
  12. ^ Mullard A (November 2020). "How COVID vaccines are being divvied up around the world". Nature. doi:10.1038/d41586-020-03370-6. PMID 33257891. S2CID 227246811.
  13. ^ a b So AD, Woo J (December 2020). "Reserving coronavirus disease 2019 vaccines for global access: cross sectional analysis". BMJ. 371: m4750. doi:10.1136/bmj.m4750. PMC 7735431. PMID 33323376.
  14. ^ a b c Gates B (30 April 2020). "The vaccine race explained: What you need to know about the COVID-19 vaccine". The Gates Notes. Archived from the original on 14 May 2020. Retrieved 2 May 2020.
  15. ^ Cavanagh D (December 2003). "Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus". Avian Pathology. 32 (6): 567–82. doi:10.1080/03079450310001621198. PMC 7154303. PMID 14676007.
  16. ^ Gao W, Tamin A, Soloff A, D'Aiuto L, Nwanegbo E, Robbins PD, et al. (December 2003). "Effects of a SARS-associated coronavirus vaccine in monkeys". Lancet. 362 (9399): 1895–96. doi:10.1016/S0140-6736(03)14962-8. PMC 7112457. PMID 14667748.
  17. ^ Kim E, Okada K, Kenniston T, Raj VS, AlHajri MM, Farag EA, et al. (October 2014). "Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice". Vaccine. 32 (45): 5975–82. doi:10.1016/j.vaccine.2014.08.058. PMC 7115510. PMID 25192975.
  18. ^ Greenough TC, Babcock GJ, Roberts A, Hernandez HJ, Thomas WD, Coccia JA, et al. (February 2005). "Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice". The Journal of Infectious Diseases. 191 (4): 507–14. doi:10.1086/427242. PMC 7110081. PMID 15655773.
  19. ^ Tripp RA, Haynes LM, Moore D, Anderson B, Tamin A, Harcourt BH, et al. (September 2005). "Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): identification of neutralizing and antibodies reactive to S, N, M and E viral proteins". Journal of Virological Methods. 128 (1–2): 21–28. doi:10.1016/j.jviromet.2005.03.021. PMC 7112802. PMID 15885812.
  20. ^ Roberts A, Thomas WD, Guarner J, Lamirande EW, Babcock GJ, Greenough TC, et al. (March 2006). "Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters". The Journal of Infectious Diseases. 193 (5): 685–92. doi:10.1086/500143. PMC 7109703. PMID 16453264.
  21. ^ a b Jiang S, Lu L, Du L (January 2013). "Development of SARS vaccines and therapeutics is still needed". Future Virology. 8 (1): 1–2. doi:10.2217/fvl.12.126. PMC 7079997. PMID 32201503.
  22. ^ "SARS (severe acute respiratory syndrome)". National Health Service. 5 March 2020. Archived from the original on 9 March 2020. Retrieved 31 January 2020.
  23. ^ Shehata MM, Gomaa MR, Ali MA, Kayali G (June 2016). "Middle East respiratory syndrome coronavirus: a comprehensive review". Frontiers of Medicine. 10 (2): 120–36. doi:10.1007/s11684-016-0430-6. PMC 7089261. PMID 26791756.
  24. ^ Butler D (October 2012). "SARS veterans tackle coronavirus". Nature. 490 (7418): 20. Bibcode:2012Natur.490...20B. doi:10.1038/490020a. PMID 23038444.
  25. ^ Modjarrad K, Roberts CC, Mills KT, Castellano AR, Paolino K, Muthumani K, et al. (September 2019). "Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial". The Lancet. Infectious Diseases. 19 (9): 1013–22. doi:10.1016/S1473-3099(19)30266-X. PMC 7185789. PMID 31351922.
  26. ^ Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS (2019). "Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus". Frontiers in Microbiology. 10: 1781. doi:10.3389/fmicb.2019.01781. PMC 6688523. PMID 31428074.
  27. ^ a b c d e f g h Le TT, Cramer JP, Chen R, Mayhew S (October 2020). "Evolution of the COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (10): 667–68. doi:10.1038/d41573-020-00151-8. PMID 32887942. S2CID 221503034.
  28. ^ a b c d e Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, Mayhew S (May 2020). "The COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (5): 305–06. doi:10.1038/d41573-020-00073-5. PMID 32273591.
  29. ^ Simpson S, Kaufmann MC, Glozman V, Chakrabarti A (May 2020). "Disease X: accelerating the development of medical countermeasures for the next pandemic". The Lancet. Infectious Diseases. 20 (5): e108–15. doi:10.1016/S1473-3099(20)30123-7. PMC 7158580. PMID 32197097.
  30. ^ a b c d Sanger DE, Kirkpatrick DD, Zimmer C, Thomas K, Wee SL (2 May 2020). "With Pressure Growing, Global Race for a Vaccine Intensifies". The New York Times. ISSN 0362-4331. Archived from the original on 11 May 2020. Retrieved 2 May 2020.
  31. ^ a b c d Steenhuysen J, Eisler P, Martell A, Nebehay S (27 April 2020). "Special Report: Countries, companies risk billions in race for coronavirus vaccine". Reuters. Archived from the original on 15 May 2020. Retrieved 2 May 2020.
  32. ^ Jeong-ho L, Zheng W, Zhou L (26 January 2020). "Chinese scientists race to develop vaccine as coronavirus death toll jumps". South China Morning Post. Archived from the original on 26 January 2020. Retrieved 28 January 2020.
  33. ^ Wee SL (4 May 2020). "China's coronavirus vaccine drive empowers a troubled industry". The New York Times. ISSN 0362-4331. Archived from the original on 4 May 2020. Retrieved 4 May 2020.
  34. ^ a b c Diamond MS, Pierson TC (May 2020). "The Challenges of Vaccine Development against a New Virus during a Pandemic". Cell Host & Microbe. 27 (5): 699–703. doi:10.1016/j.chom.2020.04.021. PMC 7219397. PMID 32407708.
  35. ^ Thorp HH (March 2020). "Underpromise, overdeliver". Science. 367 (6485): 1405. Bibcode:2020Sci...367.1405T. doi:10.1126/science.abb8492. PMID 32205459.
  36. ^ Blackwell T (20 April 2020). "COVID-19 vaccine researchers say pandemic lockdown placing many serious obstacles to their work". National Post. Archived from the original on 1 November 2020. Retrieved 3 May 2020.
  37. ^ Chen J (4 May 2020). "Covid-19 has shuttered labs. It could put a generation of researchers at risk". Stat. Archived from the original on 6 May 2020. Retrieved 4 May 2020.
  38. ^ a b c "Vaccine Safety – Vaccines". vaccines.gov. US Department of Health and Human Services. Archived from the original on 22 April 2020. Retrieved 13 April 2020.
  39. ^ a b c d "The drug development process". U.S. Food and Drug Administration (FDA). 4 January 2018. Archived from the original on 22 February 2020. Retrieved 12 April 2020.
  40. ^ a b Cohen J (June 2020). "Pandemic vaccines are about to face the real test". Science. 368 (6497): 1295–96. Bibcode:2020Sci...368.1295C. doi:10.1126/science.368.6497.1295. PMID 32554572.
  41. ^ a b Dubé E, Laberge C, Guay M, Bramadat P, Roy R, Bettinger J (August 2013). "Vaccine hesitancy: an overview". Human Vaccines & Immunotherapeutics. 9 (8): 1763–73. doi:10.4161/hv.24657. PMC 3906279. PMID 23584253.
  42. ^ Howard J, Stracqualursi V (18 June 2020). "Fauci warns of 'anti-science bias' being a problem in US". CNN. Archived from the original on 21 June 2020. Retrieved 21 June 2020.
  43. ^ "Vaccines: The Emergency Authorisation Procedure". European Medicines Agency. 2020. Archived from the original on 24 September 2020. Retrieved 21 August 2020.
  44. ^ Byrne J (19 October 2020). "Moderna COVID-19 vaccine under rolling review process in Canada, EU". BioPharma-Reporter.com, William Reed Business Media Ltd. Retrieved 25 November 2020.
  45. ^ Dangerfield K (20 November 2020). "Pfizer files for emergency use of coronavirus vaccine in U.S. – what about in Canada?". Global News. Retrieved 25 November 2020.
  46. ^ "G20 launches initiative for health tools needed to combat the coronavirus". The Globe and Mail. 25 April 2020.
  47. ^ "Access to COVID-19 Tools (ACT) Accelerator" (PDF). World Health Organization (WHO). 24 April 2020.
  48. ^ "The ACT-Accelerator: frequently asked questions (FAQ)". World Health Organization (WHO). 2020. Retrieved 16 December 2020.
  49. ^ "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization (WHO). 27 April 2020. Archived from the original on 30 April 2020. Retrieved 2 May 2020. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable. To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. [The] WHO is working to ensure that all of them have the chance of being tested at the initial stage of development. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale.
  50. ^ Abedi M (23 March 2020). "Canada to spend $192M on developing COVID-19 vaccine". Global News. Archived from the original on 9 April 2020. Retrieved 24 March 2020.
  51. ^ "Government of Canada's research response to COVID-19". Government of Canada. 23 April 2020. Archived from the original on 13 May 2020. Retrieved 4 May 2020.
  52. ^ Takada N, Satake M (2 May 2020). "US and China unleash wallets in race for coronavirus vaccine". Nikkei Asian Review. Archived from the original on 10 May 2020. Retrieved 3 May 2020.
  53. ^ Morriss E (22 April 2020). "Government launches coronavirus vaccine taskforce as human clinical trials start". Pharmafield. Archived from the original on 17 June 2020. Retrieved 3 May 2020.
  54. ^ Kuznia R, Polglase K, Mezzofiore G (1 May 2020). "In quest for vaccine, US makes 'big bet' on company with unproven technology". CNN. Archived from the original on 13 May 2020. Retrieved 2 May 2020.
  55. ^ Cohen J (May 2020). "U.S. 'Warp Speed' vaccine effort comes out of the shadows". Science. 368 (6492): 692–93. Bibcode:2020Sci...368..692C. doi:10.1126/science.368.6492.692. PMID 32409451.
  56. ^ Justin Sink, Jordan Fabian, Riley Griffin (15 May 2020). "Trump introduces 'Warp Speed' leaders to hasten COVID-19 vaccine". Bloomberg. Archived from the original on 21 May 2020. Retrieved 15 May 2020.CS1 maint: uses authors parameter (link)
  57. ^ "World Health Organization timeline – COVID-19". World Health Organization. 27 April 2020. Archived from the original on 29 April 2020. Retrieved 2 May 2020.
  58. ^ a b c Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, et al. (9 April 2020). "The COVID-19 vaccine development landscape". Nature Reviews Drug Discovery. 19 (5): 305–06. doi:10.1038/d41573-020-00073-5. ISSN 1474-1776. PMID 32273591.
  59. ^ a b Gates B (February 2020). "Responding to Covid-19: A once-in-a-century pandemic?". The New England Journal of Medicine. 382 (18): 1677–79. doi:10.1056/nejmp2003762. PMID 32109012.
  60. ^ Fauci AS, Lane HC, Redfield RR (March 2020). "Covid-19: Navigating the uncharted". The New England Journal of Medicine. 382 (13): 1268–69. doi:10.1056/nejme2002387. PMC 7121221. PMID 32109011.
  61. ^ a b Le TT, Cramer JP, Chen R, Mayhew S (4 September 2020). "Evolution of the COVID-19 vaccine development landscape". Nature Reviews Drug Discovery. 19 (10): 667–68. doi:10.1038/d41573-020-00151-8. ISSN 1474-1776. PMID 32887942. S2CID 221503034.
  62. ^ Weintraub R, Yadav P, Berkley S (2 April 2020). "A COVID-19 vaccine will need equitable, global distribution". Harvard Business Review. ISSN 0017-8012. Archived from the original on 9 June 2020. Retrieved 9 June 2020.
  63. ^ "COVID-19 pandemic reveals the risks of relying on private sector for life-saving vaccines, says expert". CBC Radio. 8 May 2020. Archived from the original on 13 May 2020. Retrieved 8 June 2020.
  64. ^ Ahmed DD (4 June 2020). "Oxford, AstraZeneca COVID-19 deal reinforces 'vaccine sovereignty'". Stat. Archived from the original on 12 June 2020. Retrieved 8 June 2020.
  65. ^ Grenfell R, Drew T (14 February 2020). "Here's why the WHO says a coronavirus vaccine is 18 months away". Business Insider. Retrieved 11 November 2020.
  66. ^ "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization. 27 April 2020. Archived from the original on 30 April 2020. Retrieved 2 May 2020. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable. To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. [The] WHO is working to ensure that all of them have the chance of being tested at the initial stage of development. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale.
  67. ^ Yamey G, Schäferhoff M, Hatchett R, Pate M, Zhao F, McDade KK (May 2020). "Ensuring global access to COVID‑19 vaccines". Lancet. 395 (10234): 1405–06. doi:10.1016/S0140-6736(20)30763-7. PMC 7271264. PMID 32243778. CEPI estimates that developing up to three vaccines in the next 12–18 months will require an investment of at least US$2 billion. This estimate includes Phase 1 clinical trials of eight vaccine candidates, progression of up to six candidates through Phase 2 and 3 trials, completion of regulatory and quality requirements for at least three vaccines, and enhancing global manufacturing capacity for three vaccines.
  68. ^ "WHO 'backed China's emergency use' of experimental Covid-19 vaccines". South China Morning Post. 25 September 2020. Archived from the original on 26 September 2020. Retrieved 26 September 2020.
  69. ^ Kramer AE (19 September 2020). "Russia Is Slow to Administer Virus Vaccine Despite Kremlin's Approval". The New York Times. ISSN 0362-4331. Archived from the original on 27 September 2020. Retrieved 28 September 2020.
  70. ^ "Pfizer and BioNTech to Submit Emergency Use Authorization Request Today to the U.S. FDA for COVID-19 Vaccine". Pfizer (Press release). 20 November 2020. Retrieved 20 November 2020.
  71. ^ Park A (20 November 2020). "Exclusive: Pfizer CEO Discusses Submitting the First COVID-19 Vaccine Clearance Request to the FDA". Time. Retrieved 20 November 2020.
  72. ^ "Information for Healthcare Professionals on Pfizer/BioNTech COVID-19 vaccine". Medicines & Healthcare products Regulatory Agency (MHRA). 8 December 2020. Retrieved 13 December 2020.
  73. ^ "Conditions of Authorisation for Pfizer/BioNTech COVID-19 vaccine". Medicines and Healthcare products Regulatory Agency (MHRA). 3 December 2020. Retrieved 19 December 2020.
  74. ^ "UK medicines regulator gives approval for first UK COVID-19 vaccine". Medicines and Healthcare Products Regulatory Agency, Government of the UK. 2 December 2020. Retrieved 2 December 2020.
  75. ^ Mueller, Benjamin (2 December 2020). "U.K. Approves Pfizer Coronavirus Vaccine, a First in the West". The New York Times. Retrieved 2 December 2020.
  76. ^ Roberts, Michelle (2 December 2020). "Covid Pfizer vaccine approved for use next week in UK". BBC. Retrieved 2 December 2020.
  77. ^ "Questions and Answers: COVID-19 vaccination in the EU". European Commission. 21 December 2020. Retrieved 21 December 2020.
  78. ^ "Bahrain second in the world to approve the Pfizer/BioNTech Covid-19 vaccine". Bahrain News Agency. 4 December 2020. Retrieved 9 December 2020.
  79. ^ "UAE: Ministry of Health announces 86 per cent vaccine efficacy". Gulf News. Retrieved 9 December 2020.
  80. ^ Thomas K, LaFraniere S, Weiland N, Goodnough A, Haberman M (12 December 2020). "F.D.A. Clears Pfizer Vaccine, and Millions of Doses Will Be Shipped Right Away". The New York Times. Retrieved 12 December 2020.
  81. ^ "FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine". U.S. Food and Drug Administration (FDA) (Press release). Retrieved 18 December 2020.
  82. ^ Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, et al. (December 2020). "The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine – United States, December 2020" (PDF). MMWR. Morbidity and Mortality Weekly Report. 69 (5152): 1653–56. doi:10.15585/mmwr.mm695152e1. PMID 33382675. S2CID 229945697.
  83. ^ Lovelace Jr B (19 December 2020). "FDA approves second Covid vaccine for emergency use as it clears Moderna's for U.S. distribution". CNBC. Retrieved 19 December 2020.
  84. ^ [1]
  85. ^ Tétrault-Farber, Maria Vasilyeva, Gabrielle (31 March 2021). "Russia registers world's first COVID-19 vaccine for animals". Reuters.
  86. ^ "Russia registers world's 1st Covid vaccine Carnivac-Cov for animals". mint. 31 March 2021.
  87. ^ Agências, Renata Monteiro. "Rússia aprova a "primeira vacina contra a covid-19" para animais". PÚBLICO (in Portuguese). Retrieved 31 March 2021.
  88. ^ "Pertama di Dunia, Rusia Buat Vaksin Corona Khusus Hewan". CNN Indonesia (in Indonesian). Retrieved 31 March 2021.
  89. ^ "Russia Registers First COVID-19 Vaccine For Animals, Greece Expresses Interest – Greek City Times". Greek City Times. Retrieved 31 March 2021.
  90. ^ Flanagan, Katie L.; Best, Emma; Crawford, Nigel W.; Giles, Michelle; Koirala, Archana; Macartney, Kristine; Russell, Fiona; Teh, Benjamin W.; Wen, Sophie CH (2020). "Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines". Frontiers in Immunology. 11: 579250. doi:10.3389/fimmu.2020.579250. ISSN 1664-3224. PMC 7566192. PMID 33123165.
  91. ^ Cross, Ryan (29 September 2020). "The tiny tweak behind COVID-19 vaccines". Chemical & Engineering News. 98 (38).
  92. ^ Krammer F (October 2020). "SARS-CoV-2 vaccines in development". Nature. 586 (7830): 516–27. Bibcode:2020Natur.586..516K. doi:10.1038/s41586-020-2798-3. PMID 32967006. S2CID 221887746.
  93. ^ Park KS, Sun X, Aikins ME, Moon JJ (February 2021). "Non-viral COVID-19 vaccine delivery systems". Advanced Drug Delivery Reviews. 169: 137–51. doi:10.1016/j.addr.2020.12.008. PMC 7744276. PMID 33340620.
  94. ^ Kowalski PS, Rudra A, Miao L, Anderson DG (April 2019). "Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery". Molecular Therapy. 27 (4): 710–28. doi:10.1016/j.ymthe.2019.02.012. PMC 6453548. PMID 30846391.
  95. ^ Verbeke R, Lentacker I, De Smedt SC, Dewitte H (October 2019). "Three decades of messenger RNA vaccine development". Nano Today. 28: 100766. doi:10.1016/j.nantod.2019.100766.
  96. ^ "COVID-19 ACIP Vaccine Recommendations". Centers for Disease Control and Prevention (CDC). Retrieved 18 February 2021.
  97. ^ "Safe COVID-19 vaccines for Europeans". European Commission – European Commission. Retrieved 19 February 2021.
  98. ^ a b c "Regulatory Decision Summary – Pfizer–BioNTech COVID-19 Vaccine". Health Canada, Government of Canada. 9 December 2020. Retrieved 9 December 2020.
  99. ^ a b "Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Adults". ClinicalTrials.gov. United States National Library of Medicine. 30 April 2020. NCT04368728. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  100. ^ a b "A Multi-site Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety and Immunogenicity of four Prophylactic SARS-CoV-2 RNA Vaccines Against COVID-19 Using Different Dosing Regimens in Healthy Adults". EU Clinical Trials Register. European Union. 14 April 2020. EudraCT 2020-001038-36. Archived from the original on 22 April 2020. Retrieved 22 April 2020.
  101. ^ a b "A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19". ClinicalTrials.gov. United States National Library of Medicine. 14 July 2020. NCT04470427. Archived from the original on 11 October 2020. Retrieved 27 July 2020.
  102. ^ a b Palca J (27 July 2020). "COVID-19 vaccine candidate heads to widespread testing in U.S." NPR. Archived from the original on 11 October 2020. Retrieved 27 July 2020.
  103. ^ a b "EMA starts rolling review of CureVac's COVID-19 vaccine (CVnCoV)". European Medicines Agency (EMA) (Press release). 1 December 2020. Retrieved 12 February 2021.
  104. ^ a b c Moghimi SM (2021). "Allergic Reactions and Anaphylaxis to LNP-Based COVID-19 Vaccines". Molecular Therapy. 29 (3): 898–900. doi:10.1016/j.ymthe.2021.01.030. PMC 7862013. PMID 33571463.
  105. ^ a b "What are viral vector-based vaccines and how could they be used against COVID-19?". GAVI. 2020. Retrieved 26 January 2021.
  106. ^ "Understanding Viral Vector COVID-19 Vaccines". U.S. Centers for Disease Control and Prevention (CD). 13 April 2021. Retrieved 19 April 2021.
  107. ^ a b c "Investigating a Vaccine Against COVID-19". ClinicalTrials.gov. United States National Library of Medicine. 26 May 2020. NCT04400838. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  108. ^ a b "A Phase 2/3 study to determine the efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19". EU Clinical Trials Register. European Union. 21 April 2020. EudraCT 2020-001228-32. Archived from the original on 5 October 2020. Retrieved 3 August 2020.
  109. ^ a b O'Reilly P (26 May 2020). "A Phase III study to investigate a vaccine against COVID-19". ISRCTN. doi:10.1186/ISRCTN89951424. ISRCTN89951424.
  110. ^ Corum J, Carl Z (8 January 2021). "How Gamaleya's Vaccine Works". The New York Times. Retrieved 27 January 2021.
  111. ^ a b "A Study of Ad26.COV2.S in Adults". ClinicalTrials.gov. 4 August 2020. Archived from the original on 16 September 2020. Retrieved 23 August 2020.
  112. ^ a b "A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants". ClinicalTrials.gov. US National Library of Medicine. Archived from the original on 26 September 2020.
  113. ^ Johnson C, McGinley L. "Johnson & Johnson seeks emergency FDA authorization for single-shot coronavirus vaccine". The Washington Post.
  114. ^ "It's not just Johnson & Johnson: China has a single-dose COVID-19 vaccine that's 65% effective". Fortune. Retrieved 28 February 2021.
  115. ^ Wu S, Zhong G, Zhang J, Shuai L, Zhang Z, Wen Z, et al. (August 2020). "A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge". Nat Commun. 11 (1): 4081. Bibcode:2020NatCo..11.4081W. doi:10.1038/s41467-020-17972-1. PMC 7427994. PMID 32796842.
  116. ^ Petrovsky N, Aguilar JC (October 2004). "Vaccine adjuvants: current state and future trends". Immunology and Cell Biology. 82 (5): 488–96. doi:10.1111/j.0818-9641.2004.01272.x. PMID 15479434. S2CID 154670.
  117. ^ a b c "Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of SARS-CoV-2 Infection (COVID-19) (Renqiu)". ClinicalTrials.gov. United States National Library of Medicine. 12 May 2020. NCT04383574. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  118. ^ a b "Clinical Trial of Efficacy and Safety of Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine in Healthcare Professionals (PROFISCOV)". ClinicalTrials.gov. United States National Library of Medicine. 2 July 2020. NCT04456595. Archived from the original on 11 October 2020. Retrieved 3 August 2020.
  119. ^ a b PT. Bio Farma (10 August 2020). "A Phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-COV-2 inactivated vaccine in healthy adults aged 18–59 years in Indonesia". Registri Penyakit Indonesia. Retrieved 15 August 2020.
  120. ^ a b c Chen W, Al Kaabi N (18 July 2020). "A Phase III clinical trial for inactivated novel coronavirus pneumonia (COVID-19) vaccine (Vero cells)". Chinese Clinical Trial Registry. Retrieved 15 August 2020.
  121. ^ Russia approves its third COVID-19 vaccine, CoviVac 20 February 2021 www.reuters.com, accessed 11 April 2021
  122. ^ a b "VLA2001 COVID-19 Vaccine". Precision Vaccinations. 31 December 2020. Retrieved 11 January 2021.
  123. ^ a b "Dose Finding Study to Evaluate Safety, Tolerability and Immunogenicity of an Inactiviated Adjuvanted Sars-Cov-2 Virus Vaccine Candidate Against Covid-19 in Healthy Adults". clinicaltrials.gov. U.S. National Library of Medicine. 30 December 2020. Retrieved 11 January 2021.
  124. ^ "Module 2 – Subunit vaccines". WHO Vaccine Safety Basics.
  125. ^ "Study of the Safety, Reactogenicity and Immunogenicity of "EpiVacCorona" Vaccine for the Prevention of COVID-19 (EpiVacCorona)". ClinicalTrials.gov. United States National Library of Medicine. 22 September 2020. NCT04368988. Retrieved 16 November 2020.
  126. ^ a b "Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrix-M Adjuvant". ClinicalTrials.gov. United States National Library of Medicine. 30 April 2020. NCT04368988. Archived from the original on 14 July 2020. Retrieved 14 July 2020.
  127. ^ a b "A Study on the Safety, Tolerability and Immune Response of SARS-CoV-2 Sclamp (COVID-19) Vaccine in Healthy Adults". ClinicalTrials.gov. United States National Library of Medicine. 3 August 2020. NCT04495933. Archived from the original on 11 October 2020. Retrieved 4 August 2020.
  128. ^ a b "UQ-CSL V451 Vaccine". precisionvaccinations.com. Retrieved 11 December 2020.
  129. ^ a b "A prospective, randomized, adaptive, phase I/II clinical study to evaluate the safety and immunogenicity of Novel Corona Virus −2019-nCov vaccine candidate of M/s Cadila Healthcare Limited by intradermal route in healthy subjects". ctri.nic.in. Clinical Trials Registry India. 15 December 2020. CTRI/2020/07/026352. Archived from the original on 22 November 2020.
  130. ^ a b "Safety, Tolerability and Immunogenicity of INO-4800 for COVID-19 in Healthy Volunteers". ClinicalTrials.gov. United States National Library of Medicine. 7 April 2020. NCT04336410. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  131. ^ a b "IVI, INOVIO, and KNIH to partner with CEPI in a Phase I/II clinical trial of INOVIO's COVID-19 DNA vaccine in South Korea". International Vaccine Institute. 16 April 2020. Retrieved 23 April 2020.
  132. ^ a b "Study of COVID-19 DNA Vaccine (AG0301-COVID19)". ClinicalTrials.gov. United States National Library of Medicine. 9 July 2020. NCT04463472. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  133. ^ a b "Safety and Immunogenicity Study of GX-19, a COVID-19 Preventive DNA Vaccine in Healthy Adults". ClinicalTrials.gov. United States National Library of Medicine. 24 June 2020. NCT04445389. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  134. ^ a b "S. Korea's Genexine begins human trial of coronavirus vaccine". Reuters. 19 June 2020. Archived from the original on 11 October 2020. Retrieved 25 June 2020.
  135. ^ a b "Safety and Immunity of Covid-19 aAPC Vaccine". ClinicalTrials.gov. United States National Library of Medicine. 9 March 2020. NCT04299724. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  136. ^ a b "Immunity and Safety of Covid-19 Synthetic Minigene Vaccine". ClinicalTrials.gov. United States National Library of Medicine. 19 February 2020. NCT04276896. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  137. ^ a b "A Phase I/II Randomized, Multi-Center, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine (IIBR-100) in Adults". ClinicalTrials.gov. United States National Library of Medicine. 1 November 2020. NCT04608305.
  138. ^ https://www.npr.org/sections/health-shots/2021/04/06/984486776/scientists-race-to-develop-next-generation-of-covid-vaccines
  139. ^ Johnson CY, Mufson S. "Can old vaccines from science's medicine cabinet ward off coronavirus?". The Washington Post. ISSN 0190-8286. Retrieved 31 December 2020.
  140. ^ "Bacille Calmette-Guérin (BCG) vaccination and COVID-19". World Health Organization (WHO). 12 April 2020. Archived from the original on 30 April 2020. Retrieved 1 May 2020.
  141. ^ "FDA Briefing Document: Pfizer–BioNTech COVID-19 Vaccine" (PDF). U.S. Food and Drug Administration. 10 December 2020. Retrieved 1 January 2021.
  142. ^ a b Zimmer C (20 November 2020). "2 Companies Say Their Vaccines Are 95% Effective. What Does That Mean? You might assume that 95 out of every 100 people vaccinated will be protected from Covid-19. But that's not how the math works". The New York Times. Retrieved 21 November 2020.
  143. ^ Branswell H (2 February 2021). "Comparing three Covid-19 vaccines: Pfizer, Moderna, J&J". Stat. Retrieved 28 February 2021.
  144. ^ Randolph HE, Barreiro LB (May 2020). "Herd Immunity: Understanding COVID-19". Immunity. 52 (5): 737–41. doi:10.1016/j.immuni.2020.04.012. PMC 7236739. PMID 32433946.
  145. ^ "The FDA's cutoff for Covid-19 vaccine effectiveness is 50 percent. What does that mean?". NBC News. Retrieved 8 January 2021.
  146. ^ "EMA sets 50% efficacy goal – with flexibility – for COVID vaccines". raps.org. Retrieved 8 January 2021.
  147. ^ Bartsch SM, O'Shea KJ, Ferguson MC, Bottazzi ME, Wedlock PT, Strych U, et al. (October 2020). "Vaccine Efficacy Needed for a COVID-19 Coronavirus Vaccine to Prevent or Stop an Epidemic as the Sole Intervention". American Journal of Preventive Medicine. 59 (4): 493–503. doi:10.1016/j.amepre.2020.06.011. PMC 7361120. PMID 32778354.
  148. ^ Dean N, Madewell Z (5 March 2021). "Understanding the spectrum of vaccine efficacy measures". The BMJ Opinion. Retrieved 10 March 2021.
  149. ^ a b c "Moderna COVID-19 Vaccine – cx-024414 injection, suspension". DailyMed. U.S. National Institutes of Health. Retrieved 20 December 2020.
  150. ^ a b "Pfizer–BioNTech COVID-19 Vaccine – rna ingredient bnt-162b2 injection, suspension". DailyMed. U.S. National Institutes of Health. Retrieved 14 December 2020.
  151. ^ "Russia okays single-dose Sputnik Light Covid-19 vaccine, has 79.4% efficacy". India Today. 6 May 2021.
  152. ^ a b Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. (February 2021). "Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia". Lancet. 397 (10275): 671–81. doi:10.1016/S0140-6736(21)00234-8. PMC 7852454. PMID 33545094.
  153. ^ a b Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. (March 2021). "Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials". Lancet. 397 (10277): 881–91. doi:10.1016/S0140-6736(21)00432-3. PMC 7894131. PMID 33617777.
  154. ^ "AZD1222 US Phase III primary analysis confirms safety and efficacy". Retrieved 25 March 2021.
  155. ^ a b "UAE says Sinopharm vaccine has 86% efficacy against COVID-19". Reuters. Dubai. 9 December 202. Retrieved 10 March 2021.
  156. ^ Wee SL, Qin A (30 December 2020). "A Chinese Covid-19 Vaccine Has Proved Effective, Its Maker Says". The New York Times. Retrieved 30 December 2020.
  157. ^ "Sinovac says COVID-19 vaccine effective in preventing hospitalization, death". Reuters. 5 February 2021. Retrieved 10 March 2021.
  158. ^ "Chile Approves Chinese Coronavirus Vaccine". Barron's. Agence France-Presse. 20 January 2021. Retrieved 10 March 2021.
  159. ^ "Summary of Clinical Trial Data of Sinovac's COVID-19 Vaccine (CoronaVac)" (Press release). Sinovac Biotech. 3 April 2021. Retrieved 12 April 2021.
  160. ^ Wadman M, Cohen J (28 January 2021). "Novavax vaccine delivers 89% efficacy against COVID-19 in UK – but is less potent in South Africa". Science. doi:10.1126/science.abg8101.
  161. ^ "Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial". Novavax Inc. (Press release). Retrieved 3 March 2021.
  162. ^ a b c d "Janssen COVID-19 Vaccine – ad26.cov2.s injection, suspension". DailyMed. U.S. National Institutes of Health. Retrieved 15 March 2021.
  163. ^ "FDA Briefing Document: Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19". US Food & Drug Administration (FDA). 26 February 2021. Retrieved 1 April 2021.
  164. ^ Kay, Chris (21 April 2021). "Homegrown Indian Covid Vaccine Already in Use Shows 78% Efficacy". Bloomberg. Retrieved 25 April 2021.
  165. ^ "Ocugen's COVID-19 Vaccine Co-Development Partner, Bharat Biotech, Shares Second Interim Results demonstrating 100% Protection against Severe Disease including Hospitalization" (Press release). Malvern, Pennsylvania: GlobeNewswire. Ocugen. 21 April 2021. Retrieved 26 April 2021.
  166. ^ a b c d Peshimam G, Farooq U (8 February 2021). "CanSinoBIO's COVID-19 vaccine 65.7% effective in global trials, Pakistan official says". Reuters. Islamabad. Retrieved 5 March 2021. its single-dose regimen and normal refrigerator storage requirement could make it a favourable option for many countries
  167. ^ "What is the difference between efficacy and effectiveness?". gavi.org. GAVI. 18 November 2020. Retrieved 21 April 2021.
  168. ^ Amir Tal; Elizabeth Cohen (29 January 2021). "Israel's health data suggests Pfizer and Moderna vaccines may be more effective than we thought". CNN. Retrieved 27 March 2021.
  169. ^ a b c "Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers – Eight U.S. Locations, December 2020–March 2021". cdc.gov. 29 March 2021.
  170. ^ a b Victoria Jane Hall, Sarah Foulkes, Ayoub Saei, Nick Andrews, Blanche Oguti, Andre Charlett, et al. (February 2021). "Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study)". SSRN 3790399.
  171. ^ a b Pfizer (11 March 2021). "Real-World Evidence Confirms High Effectiveness of Pfizer–BioNTech COVID-19 Vaccine and Profound Public Health Impact of Vaccination One Year After Pandemic Declared". Retrieved 1 April 2021.
  172. ^ Aaron J Tande; Benjamin D Pollock; Nilay D Shah; Gianrico Farrugia; Abinash Virk; Melanie Swift; Laura Breeher; Matthew Binnicker; Elie F Berbari (10 March 2021). "Impact of the COVID-19 Vaccine on Asymptomatic Infection Among Patients Undergoing Pre-Procedural COVID-19 Molecular Screening". Clinical Infectious Diseases. doi:10.1093/cid/ciab229. PMC 7989519. PMID 33704435.
  173. ^ CNN, Nectar Gan. "Chinese Covid-19 vaccine efficacy is 'not high', top health official admits". CNN. Retrieved 14 April 2021.
  174. ^ "La vacuna CoronaVac demostró ser efectiva en un 89% para evitar hospitalizaciones UCI" [CoronaVac vaccine proved to be 89% effective in preventing ICU hospitalizations] (Press release) (in Spanish). Santiago: Ministry of Health (Chile). 16 April 2021. Retrieved 18 April 2021.
  175. ^ Araos, Rafael (16 April 2021). Efectividad de la vacuna CoronaVac con virus inactivo contra SARS-CoV-2 en Chile [Effectiveness of the CoronaVac vaccine with inactivated virus against SARS-CoV-2 in Chile] (PDF) (Report) (in Spanish). Ministry of Health (Chile). p. 12-13. Retrieved 18 April 2021.
  176. ^ Estudio "Efectividad de la vacuna CoronaVac con virus inactivado contra SARS-CoV-2 en Chile"tran [Study "Effectiveness of the CoronaVac vaccine with inactivated virus against SARS-CoV-2 in Chile"] (Online video) (in Spanish). Ministry of Health (Chile). 16 April 2021. Event occurs at 10:12-13:42, 16:59-17:45. Retrieved 18 April 2021.
  177. ^ "China's Coronavac 80% effective at preventing Covid deaths: Chile results". Santiago: France 24. Agence France-Presse. 16 April 2021. Retrieved 18 April 2021.
  178. ^ "Russia's Sputnik V vaccine 97.6% effective in real-world study". Reuters. Moscow. 19 April 2021. Retrieved 21 April 2021.
  179. ^ "Sputnik V demonstrates 97.6% efficacy according to analysis of data from 3.8 million vaccinated persons in Russia making it the most efficient COVID-19 vaccine in the world" (Press release). Moscow: Russian Direct Investment Fund. 19 April 2021. Retrieved 21 April 2021.
  180. ^ a b Office of the Commissioner (23 February 2021). "Coronavirus (COVID-19) Update: FDA Issues Policies to Guide Medical Product Developers Addressing Virus Variants". FDA. Retrieved 7 March 2021.
  181. ^ Mahase E (March 2021). "Covid-19: Where are we on vaccines and variants?". BMJ. 372: n597. doi:10.1136/bmj.n597. PMID 33653708. S2CID 232093175.
  182. ^ "Inside the B.1.1.7 Coronavirus Variant". The New York Times. 18 January 2021. Retrieved 29 January 2021.
  183. ^ Muik A, Wallisch AK, Sänger B, Swanson KA, Mühl J, Chen W, et al. (March 2021). "Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera". Science. 371 (6534): 1152–53. Bibcode:2021Sci...371.1152M. doi:10.1126/science.abg6105. PMC 7971771. PMID 33514629.
  184. ^ a b Wang P, Nair MS, Liu L, Iketani S, Luo Y, Guo Y, et al. (March 2021). "Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7". Nature. 593 (7857): 130–35. doi:10.1038/s41586-021-03398-2. PMID 33684923.
  185. ^ Emary KR, Golubchik T, Aley PK, Ariani CV, Angus BJ, Bibi S, et al. (2021). "Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)". SSRN 3779160.
  186. ^ Mahase E (February 2021). "Covid-19: Novavax vaccine efficacy is 86% against UK variant and 60% against South African variant". BMJ. 372: n296. doi:10.1136/bmj.n296. PMID 33526412. S2CID 231730012.
  187. ^ a b Wang GL, Wang ZY, Duan LJ, Meng QC, Jiang MD, Cao J, et al. (April 2021). "Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization". N Engl J Med. doi:10.1056/NEJMc2103022. PMC 8063885. PMID 33822491.
  188. ^ Kuchler H (25 January 2021). "Moderna develops new vaccine to tackle mutant Covid strain". Financial Times. Retrieved 30 January 2021.
  189. ^ Liu Y, Liu J, Xia H, Zhang X, Fontes-Garfias CR, Swanson KA, et al. (February 2021). "Neutralizing Activity of BNT162b2-Elicited Serum – Preliminary Report". The New England Journal of Medicine. doi:10.1056/nejmc2102017. PMID 33596352.
  190. ^ a b Hoffmann M, Arora P, Gross R, Seidel A, Hoernich BF, Hahn AS, et al. (March 2021). "1 SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies". Cell. 184 (9): 2384–2393.e12. doi:10.1016/j.cell.2021.03.036. PMC 7980144. PMID 33794143.
  191. ^ "Pfizer and BioNTech Confirm High Efficacy and No Serious Safety Concerns Through Up to Six Months Following Second Dose in Updated Topline Analysis of Landmark COVID-19 Vaccine Study" (Press release). Pfizer. 1 April 2021. Retrieved 2 April 2021.
  192. ^ "Johnson & Johnson Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial" (Press release). Johnson & Johnson. 29 January 2021. Retrieved 29 January 2021.
  193. ^ Francis D, Andy B (6 February 2021). "Oxford/AstraZeneca COVID shot less effective against South African variant: study". Reuters. Retrieved 8 February 2021.
  194. ^ "South Africa halts AstraZeneca jab over new strain". BBC News. 7 February 2021. Retrieved 8 February 2021.
  195. ^ Booth W, Johnson CY (7 February 2021). "South Africa suspends Oxford-AstraZeneca vaccine rollout after researchers report 'minimal' protection against coronavirus variant". The Washington Post. London. Retrieved 8 February 2021. South Africa will suspend use of the coronavirus vaccine being developed by Oxford University and AstraZeneca after researchers found it provided 'minimal protection' against mild to moderate coronavirus infections caused by the new variant first detected in that country.
  196. ^ "Covid: South Africa halts AstraZeneca vaccine rollout over new variant". BBC News. 8 February 2021. Retrieved 12 February 2021.
  197. ^ Novavax (30 October 2020). "A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1 Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV". Bill and Melinda Gates Foundation. Cite journal requires |journal= (help)
  198. ^ Shinde, Vivek; et al. (3 March 2021). "Preliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant". medxriv.org. doi:10.1101/2021.02.25.21252477. S2CID 232093107.
  199. ^ Wang, Guo-Lin; Wang, Zhuang-Ye; Duan, Li-Jun; Meng, Qing-Chuan; Jiang, Ming-Dong; Cao, Jing; Yao, Lin; Zhu, Ka-Li; Cao, Wu-Chun; Ma, Mai-Juan (6 April 2021). "Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization". New England Journal of Medicine. 0. doi:10.1056/NEJMc2103022. ISSN 0028-4793. PMC 8063885. PMID 33822491.
  200. ^ "PANGO lineages". cov-lineages.org. Retrieved 18 April 2021.
  201. ^ Koshy J (8 April 2021). "Coronavirus | Indian 'double mutant' strain named B.1.617". The Hindu.
  202. ^ "India's variant-fuelled second wave coincided with spike in infected flights landing in Canada". Toronto Sun. 10 April 2021. Retrieved 10 April 2021.
  203. ^ Cherian, Sarah; Potdar, Varsha; Jadhav, Santosh; Yadav, Pragya; Gupta, Nivedita; Das, Mousmi; Rakshit, Partha; Singh, Sujeet; Abraham, Priya; Panda, Samiran (24 April 2021). ""Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India"". doi:10.1101/2021.04.22.440932. S2CID 233415787. Retrieved 25 April 2021. Cite journal requires |journal= (help)
  204. ^ Shrutirupa (17 April 2021). "IS THIS COVID – 20? | Double Mutant Strain Explained". Self Immune. Retrieved 18 April 2021.
  205. ^ "'Double mutant': What are the risks of India's new Covid-19 variant". www.bbc.co.uk/news. 25 March 2021. Retrieved 11 April 2021.
  206. ^ Haseltine WA. An Indian SARS-CoV-2 Variant Lands In California. More Danger Ahead? Forbes.com, Apr 12, 2021, accessed 14 April 2021
  207. ^ "Confirmed cases of COVID-19 variants identified in UK". Public Health England. 15 April 2021. Retrieved 16 April 2021.
  208. ^ "How flu vaccine effectiveness and efficacy are measured". Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, US Department of Health and Human Services. 29 January 2016. Archived from the original on 7 May 2020. Retrieved 6 May 2020.
  209. ^ "Principles of epidemiology, Section 8: Concepts of disease occurrence". Centers for Disease Control and Prevention, Center for Surveillance, Epidemiology, and Laboratory Services, US Department of Health and Human Services. 18 May 2012. Archived from the original on 6 April 2020. Retrieved 6 May 2020.
  210. ^ a b Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, et al. (February 2018). "Adaptive designs in clinical trials: why use them, and how to run and report them". BMC Medicine. 16 (1): 29. doi:10.1186/s12916-018-1017-7. PMC 5830330. PMID 29490655.
  211. ^ "Adaptive designs for clinical trials of drugs and biologics: Guidance for industry" (PDF). U.S. Food and Drug Administration (FDA). 1 November 2019. Archived from the original on 13 December 2019. Retrieved 3 April 2020.
  212. ^ "An international randomised trial of candidate vaccines against COVID-19: Outline of Solidarity vaccine trial" (PDF). World Health Organization (WHO). 9 April 2020. Archived (PDF) from the original on 12 May 2020. Retrieved 9 May 2020.
  213. ^ "Vaxzevria (previously COVID-19 Vaccine AstraZeneca) EPAR". European Medicines Agency (EMA).
  214. ^ "AstraZeneca & Serum Institute of India sign licensing deal for 1 million doses of Oxford vaccine". The Economic Times. Retrieved 15 June 2020.
  215. ^ "Covid-19 vaccine: Serum Institute signs up for 100 million doses of vaccines for India, low and middle-income countries". The Financial Express. 7 August 2020.
  216. ^ Walsh N, Shelley J, Duwe E, Bonnett W (27 July 2020). "The world's hopes for a coronavirus vaccine may run in these health care workers' veins". São Paulo: CNN. Archived from the original on 3 August 2020. Retrieved 3 August 2020.
  217. ^ Gallagher J, Triggle N (30 December 2020). "Covid-19: Oxford-AstraZeneca vaccine approved for use in UK". BBC. Retrieved 5 March 2020.
  218. ^ AstraZeneca COVID-19 Vaccine (PDF) (Product Monograph). AstraZeneca. 26 February 2021. 244627. Retrieved 5 March 2021.
  219. ^ "A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19". ClinicalTrials.gov. United States National Library of Medicine. 12 May 2020. NCT04383574. Archived from the original on 23 August 2020. Retrieved 26 August 2020.
  220. ^ "Trial of Oxford COVID-19 vaccine starts in Brazil". Jenner Institute. Archived from the original on 9 September 2020. Retrieved 26 August 2020.
  221. ^ "Oxford COVID-19 vaccine final trials will be held in these 17 hospitals in India". mint. 19 August 2020.
  222. ^ Farge E, Revill J (5 January 2021). "WHO recommends two doses of Pfizer COVID-19 vaccine within 21–28 days". Reuters. Geneva. Retrieved 5 March 2021.
  223. ^ Keaten J (8 January 2021). "WHO: Amid short supplies, vaccine doses can be 6 weeks apart". Associated Press. Geneva. Retrieved 6 March 2021.
  224. ^ "COVID vaccine: Moderna shots can be 6 weeks apart, WHO says". Deutsche Welle. 26 January 2021. Retrieved 6 March 2021.
  225. ^ "Coronavirus (COVID-19) Update: FDA Allows More Flexible Storage, Transportation Conditions for Pfizer–BioNTech COVID-19 Vaccine" (Press release). Food and Drug Administration (FDA). 25 February 2021. Retrieved 5 March 2021.
  226. ^ "Pfizer–BioNTech COVID-19 Vaccine EUA Fact Sheet for Healthcare Providers" (PDF). Pfizer. 25 February 2021. Retrieved 25 February 2021.
  227. ^ "Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints" (Press release). Pfizer. 18 November 2020.
  228. ^ Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. (December 2020). "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine". The New England Journal of Medicine. 383 (27): 2603–15. doi:10.1056/NEJMoa2034577. PMC 7745181. PMID 33301246.
  229. ^ FDA Review of Efficacy and Safety of Pfizer–BioNTech COVID-19 Vaccine Emergency Use Authorization Request (PDF). U.S. Food and Drug Administration (FDA) (Report). 10 December 2020. Retrieved 11 December 2020. This article incorporates text from this source, which is in the public domain.
  230. ^ Erman M (18 November 2020). "Pfizer ends COVID-19 trial with 95% efficacy, to seek emergency-use authorization". Reuters. Retrieved 18 November 2020.
  231. ^ "An Open Study of the Safety, Tolerability and Immunogenicity of the Drug "Gam-COVID-Vac" Vaccine Against COVID-19". ClinicalTrials.gov. United States National Library of Medicine. 17 June 2020. NCT04436471. Retrieved 5 March 2021.
  232. ^ Jones I, Roy P (February 2021). "Sputnik V COVID-19 vaccine candidate appears safe and effective". Lancet. 397 (10275): 642–43. doi:10.1016/S0140-6736(21)00191-4. PMC 7906719. PMID 33545098.
  233. ^ Sagdiev R, Ivanova P (16 November 2020). "Russia focuses on freeze-dried vaccine doses as transport fix". Reuters. Moscow. Retrieved 5 March 2021.
  234. ^ "Clinical Trial of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Vaccine Against COVID-19". ClinicalTrials.gov. Archived from the original on 12 September 2020. Retrieved 11 September 2020.
  235. ^ "Clinical Trial of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Vaccine Against COVID-19 in Belarus". ClinicalTrials.gov. Health Ministry of the Russian Federation. 25 September 2020. Retrieved 18 January 2021.
  236. ^ Kumar S (1 December 2020). "Sputnik-V from Russia arrives in India for clinal trials". Hindustan Times.
  237. ^ "Clinical trial: 17 volunteers given Russia's Sputnik V Covid-19 vaccine in Pune". The Indian Express. 6 December 2020.
  238. ^ "Clinical Trial of the Immunogenicity, Safety, and Efficacy of the Gam-COVID-Vac Vaccine Against COVID-19 in Venezuela". ClinicalTrials.gov. Health Ministry of the Russian Federation. 24 November 2020. Retrieved 18 January 2021.
  239. ^ "Clinical Trial of the Immunogenicity, Safety, and Efficacy of the Gam-COVID-Vac Vaccine Against COVID-19 in Venezuela". ClinicalTrials.gov. Health Ministry of the Russian Federation. 24 November 2020. Retrieved 18 January 2021.
  240. ^ "UAE begins trials of Russia's Sputnik V Covid-19 vaccine". Clinical Trials Arena. 8 January 2021.
  241. ^ "Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19)". ClinicalTrials.gov. United States National Library of Medicine. 16 March 2020. NCT04283461. Retrieved 5 March 2021.
  242. ^ "WHO experts issue recommendations on Moderna COVID-19 vaccine". Reuters. Geneva. 26 January 2021. Retrieved 5 March 2021.
  243. ^ Fact Sheet for Healthcare Providers Administering Vaccine (Fact sheet). Food and Drug Administration. December 2020. Retrieved 5 March 2021.
  244. ^ "Promising Interim Results from Clinical Trial of NIH-Moderna COVID-19 Vaccine". National Institutes of Health (NIH). 15 November 2020.
  245. ^ Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. (February 2021). "Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine". The New England Journal of Medicine. 384 (5): 403–16. doi:10.1056/NEJMoa2035389. PMC 7787219. PMID 33378609.
  246. ^ Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. (January 2021). "Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial". The Lancet. Infectious Diseases. 21 (1): 39–51. doi:10.1016/S1473-3099(20)30831-8. PMC 7561304. PMID 33069281.
  247. ^ Elbahrawy F, Lyu D, Omar A, Che C, Paton J (9 December 2020). "China State-Backed Covid Vaccine Has 86% Efficacy, UAE Says". Bloomberg News. Retrieved 5 March 2020. CNBG's vaccine can be transported and stored at normal refrigerated temperatures.
  248. ^ Wee SL, Qin A (30 December 2020). "A Chinese Covid-19 Vaccine Has Proved Effective, Its Maker Says". The New York Times. Retrieved 30 December 2020.
  249. ^ Yang Y. "A Study to Evaluate The Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above". ClinicalTrials.gov. Archived from the original on 14 September 2020. Retrieved 15 September 2020.
  250. ^ "Clinical Trial to Evaluate the Efficacy, Immunogenicity and Safety of the Inactivated SARS-CoV-2 Vaccine (COVID-19)". ClinicalTrials.gov. Retrieved 28 September 2020.
  251. ^ "A Phase III clinical trial for inactivated novel coronavirus pneumonia (COVID-19) vaccine (Vero cells)". chictr.org.cn. Chinese Clinical Trial Register (ChiCTR). Retrieved 15 December 2020.
  252. ^ "Bahrain allows Sinopharm COVID-19 vaccine candidate use in frontline workers". MSN. Reuters. Retrieved 3 November 2020.
  253. ^ Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19 (Briefing). Food and Drug Administration. 26 February 2021. p. 6. Retrieved 6 March 2021. The vaccine, known as Ad26.COV2.S, is a replication-incompetent adenovirus type 26 (Ad26) vectored vaccine encoding a stabilized variant of the SARS-CoV-2 S protein.
  254. ^ a b Ledford H (January 2021). "J&J's one-shot COVID vaccine offers hope for faster protection". Nature. doi:10.1038/d41586-021-00119-7. PMID 33526898.
  255. ^ "Johnson & Johnson Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial" (Press release). Johnson & Johnson. 29 January 2021. Retrieved 29 January 2021.
  256. ^ "Sinovac says COVID-19 vaccine effective in preventing hospitalization, death". Reuters. 5 February 2021. Retrieved 5 March 2021.
  257. ^ Costa, Anna (11 April 2021). "Estudo clínico que comprova maior eficácia da Coronavac é enviado para Lancet" [Clinical study proving greater efficacy of Coronavac is submitted to The Lancet]. CNN Brasil (in Portuguese). São Paulo. Retrieved 12 April 2021.
  258. ^ Tan Y (14 January 2021). "Covid: What do we know about China's coronavirus vaccines?". BBC. Retrieved 5 March 2020.
  259. ^ Daily Sabah with Agencies (25 December 2020). "Turkey set to receive 'effective' COVID-19 vaccine amid calls for inoculation". Daily Sabah. Retrieved 12 February 2021.
  260. ^ Vergara, Eva. "Big Chile study finds Chinese vaccine slashes COVID deaths". ABC News. Associated Press. Retrieved 18 April 2021.
  261. ^ "Estudo clínico que comprova maior eficácia da Coronavac é enviado para Lancet". CNN Brasil (in Portuguese). Retrieved 18 April 2021.
  262. ^ "Tests show coronavirus vaccine by China's Sinovac is safe, says Brazil's Butantan Institute". Archived from the original on 29 October 2020. Retrieved 29 October 2020.
  263. ^ "Chile initiates clinical study for COVID-19 vaccine". Archived from the original on 11 October 2020. Retrieved 29 October 2020.
  264. ^ "Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial For Evaluation of Efficacy and Safety of SARS-CoV-2 Vaccine (Vero Cell), Inactivated". ClinicalTrials.gov. 8 October 2020. Archived from the original on 20 October 2020. Retrieved 22 October 2020.
  265. ^ "Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) for COVID-19 in Healthy Volunteers". ClinicalTrials.gov. NCT04471519.
  266. ^ a b "Covishield and Covaxin: What we know about India's Covid-19 vaccines". BBC. 4 March 2021. Retrieved 5 March 2020. The two doses are given four weeks apart. The vaccine can be stored at 2C to 8C.
  267. ^ "An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers". ClinicalTrials.gov. NCT04641481. Retrieved 26 November 2020.
  268. ^ "Bharat Biotech Recruits 23,000 Volunteers For Covaxin's Phase 3 Clinical Trial". NDTV.com. 28 December 2020. Retrieved 3 January 2021.
  269. ^ Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, et al. (March 2021). "Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial". Lancet Infect Dis. doi:10.1016/S1473-3099(21)00070-0. PMID 33705727. S2CID 232207293.
  270. ^ "Covaxin showed 81% interim efficacy: Bharat Biotech on Phase 3 results". Business Standard India. 3 March 2021.
  271. ^ Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. (August 2020). "Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial". Lancet. 396 (10249): 479–88. doi:10.1016/s0140-6736(20)31605-6. PMC 7836858. PMID 32702299. Lay summary.
  272. ^ "Clinical Trial of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Against COVID-19". ClinicalTrials.gov. United States National Library of Medicine. 13 November 2020. NCT04540419. Retrieved 17 November 2020.
  273. ^ Lazcano P (15 November 2020). "Así funcionan las cuatro vacunas que se probarán en Chile". La Tercera. Retrieved 15 December 2020.
  274. ^ Martinez AI (3 November 2020). "CanSino Biologics delivers COVID-19 vaccine to Mexico for late-stage trial". Reuters. Retrieved 4 November 2020.
  275. ^ Ng E (28 October 2020). "China's CanSino trials Covid-19 vaccine in 'high disease burden' nations". South China Morning Post. Retrieved 4 November 2020.
  276. ^ Nafisa E (9 August 2020). "CanSino to start Phase III trial of COVID-19 vaccine in Saudi". Reuters. Retrieved 4 November 2020.
  277. ^ Gou J. "Phase III Trial of A COVID-19 Vaccine of Adenovirus Vector in Adults 18 Years Old and Above". ClinicalTrials.gov. Archived from the original on 18 September 2020. Retrieved 17 September 2020.
  278. ^ a b c Ryzhikov AB, Ryzhikov EA, Bogryantseva MP, Usova SV, Danilenko ED, Nechaeva EA, Pyankov OV, Pyankova OG, Gudymo AS, Bodnev SA, Onkhonova GS, Sleptsova ES, Kuzubov VI, Ryndyuk NN, Ginko ZI, Petrov VN, Moiseeva AA, Torzhkova PY, Pyankov SA, Tregubchak TV, Antonec DV, Gavrilova EV, Maksyutov RA (2021). "A single blind, placebo-controlled randomized study of the safety, reactogenicity and immunogenicity of the "EpiVacCorona" Vaccine for the prevention of COVID-19, in volunteers aged 18–60 years (Phase I–II)". Russian Journal of Infection and Immunity. 11 (2): 283–96. doi:10.15789/2220-7619-ASB-1699.
  279. ^ Ryzhikov AB, Ryzhikov EA, Bogryantseva MP, Usova SV, Danilenko ED, Imatdinov IR, Nechaeva EA, Pyankov OV, Pyankova OG, Gudymo AS, Bodnev SA, Onkhonova GS, Sleptsova ES, Kuzubov VI, Ryndyuk NN, Ginko ZI, Petrov VN, Moiseeva AA, Torzhkova PY, Pyankov SA, Tregubchak TV, Antonec DV, Sleptsova ES, Gavrilova EV, Maksyutov RA (2021). "Immunogenicity and Protectivityof the Peptide Vaccine againstSARS-CoV-2". Annals of the Russian Academy of Medical Sciences. 76 (1): 5–19. doi:10.15690/vramn1528.
  280. ^ Benedyczak J (12 February 2021). Russia's Problems in the Vaccine Race (Bulletin). Polish Institute of International Affairs. Retrieved 6 March 2021. the Sputnik V and EpiVacCorona can be transported and stored at temperatures of +2 to + 8° C
  281. ^ "Russian EpiVacCorona Vaccine Has No Adverse Effects". Oreanda News. 13 January 2021.
  282. ^ a b "A Phase III Clinical Trial to Determine the Safety and Efficacy of ZF2001 for Prevention of COVID-19". ClinicalTrials.gov.
  283. ^ "China's CAS COVID-19 vaccine induces immune response in mid-stage tests". Reuters. Beijing. 23 December 2020. Retrieved 8 March 2021.
  284. ^ Yang, Shilong; Li, Yan; Dai, Lianpan; Wang, Jianfeng; He, Peng; Li, Changgui; et al. (24 March 2021). "Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials". The Lancet Infectious Diseases. doi:10.1016/S1473-3099(21)00127-4. ISSN 1473-3099. PMC 7990482. PMID 33773111.
  285. ^ Pinghui Z (20 November 2020). "Fifth Chinese Covid-19 vaccine candidate ready to enter phase 3 trials". South China Morning Post. Retrieved 26 December 2020.
  286. ^ Ying TP (7 December 2020). "MYEG to conduct phase 3 clinical trial for China's Covid-19 vaccine in Msia". New Straits Times. Retrieved 28 December 2020.
  287. ^ a b China National Biotec Group Company Limited (29 October 2020). "Multicenter, Randomized, Double Blind, Parallel Placebo Controlled, Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above". G42 Healthcare company, Abu Dhabi Health Services Company, Wuhan Institute of Biological Products Co., Ltd, Beijing Institute of Biological Products Co Ltd. Cite journal requires |journal= (help)
  288. ^ a b Universidad Peruana Cayetano Heredia (29 October 2020). "Ensayo Clínico de Fase III, Aleatorio, Doble Ciego y Controlado Con Placebo Paralelo, Para Evaluar la Seguridad y la Eficacia Protectora de la Vacuna Inactivada Contra el SARS-CoV-2 en la Población Sana de 18 años o más, en Perú". National University of San Marcos, Peru. Cite journal requires |journal= (help)
  289. ^ "Two Chinese-developed COVID-19 vaccines under review". National Medical Products Administration. 25 February 2021. Retrieved 11 April 2021.
  290. ^ Xia, Shengli; Duan, Kai; Zhang, Yuntao; Zhao, Dongyang; Zhang, Huajun; Xie, Zhiqiang; Li, Xinguo; Peng, Cheng; Zhang, Yanbo; Zhang, Wei; Yang, Yunkai (8 September 2020). "Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials". JAMA. 324 (10): 951–960. doi:10.1001/jama.2020.15543. ISSN 0098-7484. PMC 7426884. PMID 32789505.
  291. ^ "Chinese Clinical Trial Register (ChiCTR) – The world health organization international clinical trials registered organization registered platform". www.chictr.org.cn. Retrieved 1 April 2021.
  292. ^ "Briefing with Deputy Prime Minister Tatyana Golikova, Health Minister Mikhail Murashko and Head of Rospotrebnadzor Anna Popova". Government of Russia. 18 January 2021. Retrieved 20 February 2021.
  293. ^ Ryumin A (20 February 2021). "Russia registers its third COVID-19 vaccine CoviVac". TASS. Moscow. Retrieved 6 March 2021.
  294. ^ a b Ivanova P (8 February 2021). "Russia approves its third COVID-19 vaccine, CoviVac". Reuters. Moscow. Retrieved 5 March 2021. 'The CoviVac shot is given in two doses, 14 days apart. It is transported and stored at normal fridge temperatures, of 2 to 8 degrees Celsius (35.6 to 46.4 Fahrenheit),' Deputy Prime Minister Tatiana Golikova said in a government briefing in January.
  295. ^ "Центр Чумакова обнародовал сроки третьей фазы испытаний вакцины против COVID-19". govoritmoskva.ru (in Russian). Retrieved 19 April 2021.
  296. ^ Yergaliyeva A (20 December 2020). "Kazakhstan Begins Vaccinating 3,000 Volunteers With Self-Made QazCovid-in". The Astana Times. Retrieved 2 March 2021.
  297. ^ Meyer, David (26 April 2021). "A new vaccine on the scene: Kazakhstan begins rollout of homegrown QazVac". Fortune. Retrieved 26 April 2021.
  298. ^ Gotev, Georgi (23 April 2021). "Kazakhstan launches QazVac, its own COVID-19 vaccine". www.euractiv.com.
  299. ^ a b "Immunogenicity, Efficacy and Safety of QazCovid-in COVID-19 Vaccine – Full Text View – ClinicalTrials.gov". clinicaltrials.gov.
  300. ^ "Russia Approves Single-Dose Sputnik Light Covid Vaccine For Use". NDTV Coronavirus. 6 May 2021.
  301. ^ a b c "Study to Evaluate Efficacy, Immunogenicity and Safety of the Sputnik-Light (SPUTNIK-LIGHT)". clinicaltrials.gov.
  302. ^ "Single dose vaccine, Sputnik Light, authorized for use in Russia" (Press release). Russian Direct Investment Fund. 6 May 2021. Retrieved 7 May 2021.
  303. ^ Leo, Leory (7 May 2021). "Russia OKs single-dose Sputnik Light vaccine". Mint.
  304. ^ "COVID-19 vaccine tracker (Choose vaccines tab, apply filters to view select data)". Milken Institute. 8 December 2020. Retrieved 11 December 2020. Lay summary.
  305. ^ "Draft landscape of COVID 19 candidate vaccines". World Health Organization (WHO). 10 December 2020. Retrieved 11 December 2020.
  306. ^ "Hope to launch Covovax by September, says Serum Institute CEO". mint. 27 March 2021. Retrieved 28 March 2021.
  307. ^ Wadman M (November 2020). "The long shot". Science. 370 (6517): 649–53. Bibcode:2020Sci...370..649W. doi:10.1126/science.370.6517.649. PMID 33154120.
  308. ^ Wadman M (28 December 2020). "Novavax launches pivotal U.S. trial of dark horse COVID-19 vaccine after manufacturing delays". Science. doi:10.1126/science.abg3441.
  309. ^ Parekh N (24 July 2020). "Novavax: A SARS-CoV-2 Protein Factory to Beat COVID-19". Archived from the original on 22 November 2020. Retrieved 24 July 2020.
  310. ^ Chung YH, Beiss V, Fiering SN, Steinmetz NF (October 2020). "COVID-19 Vaccine Frontrunners and Their Nanotechnology Design". ACS Nano. 14 (10): 12522–37. doi:10.1021/acsnano.0c07197. PMC 7553041. PMID 33034449.
  311. ^ Moitra P, Alafeef M, Dighe K, Frieman MB, Pan D (June 2020). "Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles". ACS Nano. 14 (6): 7617–27. doi:10.1021/acsanm.0c01978. PMC 7482545. PMID 32437124.
  312. ^ "A Study Looking at the Effectiveness, Immune Response, and Safety of a COVID-19 Vaccine in Adults in the United Kingdom". ClinicalTrials.gov. Retrieved 22 November 2020.
  313. ^ "A Study Looking at the Efficacy, Immune Response, and Safety of a COVID-19 Vaccine in Adults at Risk for SARS-CoV-2". ClinicalTrials.gov. Retrieved 30 December 2020.
  314. ^ "Covovax trials begin in India, launch hopefully in September: Adar Poonawalla". India Today. 27 March 2021. Retrieved 28 March 2021.
  315. ^ Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. (December 2020). "Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine". The New England Journal of Medicine. 383 (24): 2320–32. doi:10.1056/NEJMoa2026920. PMC 7494251. PMID 32877576.
  316. ^ "Trudeau Signs Deal to Make Novavax Covid-19 Vaccine in Canada". Bloomberg.com. 2 February 2021. Retrieved 1 April 2021.
  317. ^ "EMA starts rolling review of Novavax's COVID-19 vaccine (NVX-CoV2373)". European Medicines Agency (EMA) (Press release). 1 December 2020. Retrieved 12 February 2021.
  318. ^ "Ukraine secures 12 million AstraZeneca, Novavax COVID-19 vaccine doses". Reuters. 5 February 2021. Retrieved 24 February 2021.
  319. ^ "COVID-19: Ukraine set to launch coronavirus vaccination programme". euronews. 8 February 2021. Retrieved 24 February 2021.
  320. ^ "AstraZeneca and Novavax COVID Vaccines: What We Know So Far". NBC Chicago. Retrieved 1 April 2021.
  321. ^ "UK secures deal to bottle 60m Novavax vaccine doses in the North East". CityAM. 29 March 2021. Retrieved 1 April 2021.
  322. ^ "Novavax COVID vaccine takes first step toward Australian approval". www.raps.org. Retrieved 1 April 2021.
  323. ^ biopharma-reporter.com. "New Zealand secures COVID-19 vaccines from Novavax and AstraZeneca". biopharma-reporter.com. Retrieved 1 April 2021.
  324. ^ https://www.reuters.com/business/healthcare-pharmaceuticals/skorea-says-novavax-sputnik-v-covid-19-vaccines-submitted-regulatory-approval-2021-04-29/
  325. ^ "Study of Recombinant Protein Vaccine with Adjuvant against COVID-19 in Adults 18 Years of Age and Older". pactr.samrc.ac.za. Pan African Clinical Trials Registry. Retrieved 24 March 2021.
  326. ^ "Study of Recombinant Protein Vaccine Formulations Against COVID-19 in Healthy Adults 18 Years of Age and Older". clinicaltrials.gov. United States National Library of Medicine. Retrieved 11 March 2021.
  327. ^ "Study of Recombinant Protein Vaccine With Adjuvant Against COVID-19 in Adults 18 Years of Age and Older (VAT00002)". clinicaltrials.gov. United States National Library of Medicine. Retrieved 11 March 2021.
  328. ^ "Sanofi and GSK confirm agreement with European Union to supply up to 300 million doses of adjuvanted COVID-19 vaccine". GSK (Press release). Retrieved 1 April 2021.
  329. ^ "Sanofi and GSK sign agreements with the Government of Canada to supply up to 72 million doses of adjuvanted COVID-19 vaccine". GSK (Press release). Retrieved 1 April 2021.
  330. ^ "U.S. Likely to Get Sanofi Vaccine First If It Succeeds". Bloomberg.com. 13 May 2020. Retrieved 1 April 2021.
  331. ^ "Coronavirus vaccine: UK signs deal with GSK and Sanofi". BBC News. 29 July 2020. Retrieved 1 April 2021.
  332. ^ "COVID-19". CureVac. Retrieved 21 December 2020.