COVID-19 vaccine

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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, 13 vaccines were authorized by at least one national regulatory authority for public use: two RNA vaccines (the Pfizer–BioNTech vaccine and the Moderna vaccine), five conventional inactivated vaccines (BBIBP-CorV, CoronaVac, Covaxin, WIBP-CorV and CoviVac), four viral vector vaccines (Sputnik V, the Oxford–AstraZeneca vaccine, Convidecia, and the Johnson & Johnson vaccine), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer).[3] In total, as of March 2021, 308 vaccine candidates were 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] Stanley Plotkin and Neal Halsey wrote an article published by Oxford Clinical Infectious Diseases that urged single dose interim use in order to extend vaccination to as many people as possible until vaccine availability improved.[5] Several other articles and media provided evidence for delaying 2nd doses in the same line of reasoning.[6][7][8]

As of 30 March 2021, 574.25 million doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies.[9] AstraZeneca-Oxford 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 10 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

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 a coronavirus was isolated in December 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]

On March 31, 2021, the Russian government announced that they had registered the first COVID-19 vaccine for animals.[84][85][86][87][88]

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

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] 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.[89][90][91][92]

RNA vaccines were the first COVID-19 vaccines to be authorized in the United States and the European Union.[93][94] As of January 2021, authorized vaccines of this type are the Pfizer–BioNTech COVID-19 vaccine[95][96][97] and the Moderna COVID-19 vaccine.[98][99] As of February 2021, the CVnCoV RNA vaccine from CureVac is awaiting authorization in the EU.[100]

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.[101] For 4,041,396 Moderna COVID-19 vaccine dose administrations in December 2020 and January 2021, only 10 cases of anaphylaxis were reported.[101] The lipid nanoparticles were most likely responsible for the allergic reactions.[101]

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.[102] 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.[102]

As of January 2021, authorized vaccines of this type are the British Oxford–AstraZeneca COVID-19 vaccine,[103][104][105] Russian Sputnik V,[106] Chinese Convidecia, and the Johnson & Johnson COVID-19 vaccine.[107][108]

Convidecia and Johnson & Johnson's vaccines are both one-shot vaccines which offer less complicated logistics; and can be stored under ordinary refrigeration for several months.[109][110]

Sputnik V uses Ad26 for the first dose, which is the same as the Johnson & Johnson vaccine's only dose, and Ad5 for the 2nd dose. This is the same as Convidecia, with similar single dose effectiveness and a full trial taking place on single dose effectiveness.

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.[111]

As of January 2021, authorized vaccines of this type are the Chinese CoronaVac,[112][113][114] BBIBP-CorV,[115] and WIBP-CorV; the Indian Covaxin; and the Russian CoviVac.[116] Vaccines in clinical trials include the Valneva COVID-19 vaccine.[117][118]

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.[119]

As of April 2021, the two authorized vaccines of this type are the peptide vaccine EpiVacCorona[120] and RBD-Dimer.[3] Vaccines with pending authorizations include the Novavax COVID-19 vaccine,[121] 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.[122][123]

Other types

Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines,[124][125][126][127][128][129] at least two lentivirus vector vaccines,[130][131] a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.[132]

Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID‑19 infection.[133] 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.[134]

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)[135]

The effectiveness of a new vaccine is defined by its efficacy during clinical trials.[136] The efficacy is the risk of getting the disease by vaccinated participants in the trial compared with the risk of getting the disease by unvaccinated participants.[136] 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.[137] 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.[138] 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.[139][140] 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.[141]

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. The trial location also affects the reported efficacy because different countries have different prevalences of SARS-CoV-2 variants. Ranges below are 95% confidence intervals unless indicated otherwise, and all values are for all participants regardless of age. Efficacy against severe COVID-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority.[142] 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 [143]
Pfizer–BioNTech 95% (9098%)[F] Not reported Not reported Multinational [144]
Sputnik V 92% (8695%) 100% (94100%) 100% Russia [145]
Oxford–AstraZeneca 81% (6091%)[G] 100% (97.5% CI, 72100%) 100% Multinational [146]
76% (6882%)[H] 100% 100% United States [147]
BBIBP-CorV 79% 100%[148][unreliable medical source?] 100%[148][unreliable medical source?] Multinational [149][unreliable medical source?]
CoronaVac 78% 100% 100% Brazil [150][151][152][unreliable medical source?]
Novavax 89% (7595%) 100%[I] 100%[I] United Kingdom [153][154]
60% (2080%) 100%[I] 100%[I] South Africa
Johnson & Johnson 66% (5575%)[J][K] 85% (5497%)[K] 100%[K][L] Multinational [155]
72% (5882%)[J][K] 86% (−9 to 100%)[K] 100%[K][L] United States
68% (4981%)[J][K] 88% (8100%)[K] 100%[K][L] Brazil
64% (4179%)[J][K] 82% (4695%)[K] 100%[K][L] South Africa
Covaxin 81% Not reported Not reported India [157][158][unreliable medical source?]
Convidecia 66% 91% Not reported Multinational [159][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).[143]
  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 30 severe cases reported in the placebo group (incidence rate 9.1 per 1000 person-years).[143]
  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 7 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.[144]
  7. ^ With 12 weeks or more of interval between doses. For an interval of less than 6 weeks, the trial found an efficacy ≈55% (3370%).
  8. ^ With a 4 week interval between doses. Efficacy is "at preventing symptomatic COVID-19."
  9. ^ a b c d No cases detected in trial.
  10. ^ a b c d Moderate cases.
  11. ^ 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.[155]
  12. ^ 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)[155] and 7 COVID-19 related deaths for the same placebo group.[156]

Real-world studies of vaccine 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.

  • In Israel, among the 715,425 individuals vaccinated by the Moderna/Pfizer vaccine during December 20 to January 28, 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.[160]
  • Pfizer 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%.[161]
  • A study of United Kingdom health care workers, found that the Pfizer vaccine reduced all infections, including asymptomatic, by 86%.[162]
  • A study of the general population in Israel found that the Pfizer vaccine reduced asymptomatic infection by 94%.[163]
  • 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.[164]

Variants

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.[165] Trials indicate many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19.[166] 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.[165]


B.1.1.7 variant

In December 2020, a new SARS‑CoV‑2 variant, B.1.1.7, was identified in the UK.[167] Early results suggest protection to the UK variant from the Pfizer and Moderna vaccines.[168][169] One study indicated that the Oxford–AstraZeneca vaccine had an efficacy of 42–89% against the B.1.1.7 variant, versus 71–91% against non-B.1.1.7 variants.[170] Preliminary data from a clinical trial indicated that the Novavax vaccine was ~96% effective for symptoms against the original variant, ~86% against B.1.1.7, and ~60% against the "South African" B.1.351 variant.[171]

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).[172] 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.[173] Decreased neutralizing activity of sera from patients vaccinated with Moderna and Pfizer vaccines against B.1.351 was latter confirmed by several studies.[169][174] 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.[175]

In January, 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.[176]

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.[177] 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.[178] On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of around 1 million doses of the vaccine whilst they examine the data and await advice on how to proceed.[179][180]

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.[174]

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][181][182]

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.[183][184] 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.[183][185]

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 authorities.

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)[186][a][b][103][104][105]
University of Oxford, AstraZeneca, CEPI
United Kingdom, Sweden Adenovirus vector (ChAdOx1)[103] 2 doses
4–12 weeks[190]
2–8 °C[191] Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity.[192]
Overall efficacy of 76% after the first dose and 81% after a second dose taken 12 weeks or more after the first.[146]
May 2020 – Aug 2021, Brazil (5,000),[193] United Kingdom, India[194]
Full (1)
Emergency (101)
Pfizer–BioNTech COVID-19 vaccine (Comirnaty)[95][96][97]
BioNTech, Pfizer
United States, Germany RNA (modRNA in lipid nanoparticles)[95] 2 doses
3–4 weeks[195][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[200] and published on 10 December 2020 reporting an overall efficacy of 95%.[201][202]
Jul – Nov 2020,[203][136] Germany, United States
Full (5)
Emergency (101)
Sputnik V COVID-19 vaccine (Gam-COVID-Vac)
Gamaleya Research Institute of Epidemiology and Microbiology
Russia Adenovirus vector (recombinant Ad5 and Ad26)[204] 2 doses
3 weeks[205]
−18 °C[e]
(freezer)
Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety.[207]
Interim analysis from the trial was published in The Lancet, indicating 91.6% efficacy without unusual side effects.[145]
Aug 2020 – May 2021, Russia, Belarus,[208] India,[209][210] Venezuela,[211][212] UAE[213]
Full (1)
Emergency (61)
BBIBP-CorV[115]
Sinopharm: Beijing Institute of Biological Products
China Inactivated SARS‑CoV‑2 (vero cells)[115] 2 doses
3–4 weeks[214]
2–8 °C[215] Phase III (48,000)
Randomized, double-blind, parallel placebo-controlled, to evaluate safety and protective efficacy.
Sinopharm's internal analysis indicated a 79% efficacy.[216]
Jul 2020 – Jul 2021, United Arab Emirates, Bahrain, Jordan,[217] Argentina,[218] Morocco,[219] Peru[220]
Full (4)
Emergency (38)
Moderna COVID-19 vaccine[98][99]
Moderna, NIAID, BARDA, CEPI
United States RNA (modRNA in lipid nanoparticles)[221] 2 doses
4 weeks[222][c]
−20±5 °C[223]
(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[224] and published on 30 December 2020 reporting an overall efficacy of 94%.[225]
Jul 2020 – Oct 2022, United States
Full (2)
Emergency (40)
Johnson & Johnson COVID-19 vaccine[107][108]
Janssen Vaccines (Johnson & Johnson), BIDMC
United States, Netherlands Adenovirus vector (recombinant Ad26)[226] 1 dose[227] 2–8 °C[227] 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.[228][155]
Jul 2020 – 2023, United States, Argentina, Brazil, Chile, Colombia, Mexico, Peru, the Philippines, South Africa, Ukraine
Full (0)
Emergency (42)
CoronaVac[112][113][114]
Sinovac
China Inactivated SARS‑CoV‑2 (vero cells)[112] 2 doses
2 weeks[229]
2–8 °C[230] 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%.[231] Additional results were announced by Indonesia with an efficacy of 65.3%.[232] Brazil announced results showing 50.4% effective at preventing symptomatic infections, 78% effective in preventing mild cases, and 100% effective in preventing severe cases.[233]
July 2020 – Oct 2021, Brazil (15,000);[234] Aug 2020 – January 2021, Indonesia (1,620); Chile (3,000);[235] Turkey (13,000)[236]
Full (1)
Emergency (27)
BBV152 (Covaxin)
Bharat Biotech, Indian Council of Medical Research
India Inactivated SARS‑CoV‑2 (vero cells)[237] 2 doses
4 weeks[238]
2–8 °C[238] Phase III (25,800)
Randomised, observer-blinded, placebo-controlled[239]
The interim efficacy rate is 81% as per third phase trial.[240] All data from the animal, first, second phase trials have been made public through peer-reviewed journals.[241] Phase-3 trials had shown 81% efficacy.[242]
Nov 2020 – Mar 2021, India.
Full (0)
Emergency (9)
Ad5-nCoV (Convidecia)
CanSino Biologics, Beijing Institute of Biotechnology of the Academy of Military Medical Sciences
China Adenovirus vector (recombinant Ad5)[243] 1 dose[159] 2–8 °C[159] 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.[159]
Mar–Dec 2020, China; Sep 2020 – Dec 2021, Pakistan; Sep  – Nov 2020, Russia,[244] China, Argentina, Chile;[245] Mexico;[246] Pakistan;[247] Saudi Arabia[248][249]
Full (1)
Emergency (5)
EpiVacCorona[250]
Vector Institute
Russia Subunit (peptide)[250] 2 doses
3 weeks[250]
2–8 °C[251] Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety
Nov 2020 – Dec 2021, Russia[252]
Full (1)
Emergency (2)
ZF2001 (RBD-Dimer)[3]
Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.
China Subunit (recombinant) 3 doses
30 days[253][254]
Phase III (29,000)
Randomized, double-blind, placebo-controlled[253]
Dec 2020 – Apr 2022, China, Ecuador, Indonesia, Malaysia, Pakistan, Uzbekistan[255][256]
Full (0)
Emergency (2)
WIBP-CorV
Sinopharm: Wuhan Institute of Biological Products
China Inactivated SARS‑CoV‑2 (Vero cell) 1 dose[citation needed] Phase III (51,600)
Randomized, double-blind, placebo-controlled[257]
Jul 2020 – Mar 2021, Bahrain, Egypt, Jordan, United Arab Emirates;[258] Sep 2020 – Sep 2021, Peru;[259] Sep 2020 – Dec 2020, Morocco[260]
Full (0)
Emergency (2)
CoviVac[261]
The Chumakov Centre at the Russian Academy of Sciences
Russia Inactivated SARS‑CoV‑2[262] 2 doses
2 weeks[263]
2–8 °C[263] Phase III (3,000)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
Full (0)
Emergency (1)

Vaccine candidates in human trials

COVID‑19 candidate vaccines in Phase I–III trials[3][264][265]
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)[121][266]
Novavax, CEPI
United States Subunit[267][268][269]/virus-like particle[270][271] (SARS‑CoV‑2 recombinant spike protein nanoparticle with adjuvant) Phase III (45,000)
Randomised, observer-blinded, placebo-controlled trial[272]
Sep 2020 – Jan 2021, UK (15,000); December 2020 – Mar 2021, US, Mexico, (30,000);[273] India[274]
Phase I–II (131)
IgG and neutralizing antibody response with adjuvant after booster dose.[275]
Emergency (7)
Sanofi–GSK COVID-19 vaccine (VAT00002)
Sanofi Pasteur, GSK
France, United Kingdom Subunit Phase III (34,520)[284]
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
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.[285]
Phase IIb (720): Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine With AS03 Adjuvant in Adults 18 Years of Age and Older.[286]
Sep 2020 – Sep 2022, United States
Emergency (4)
CureVac COVID-19 vaccine (CVnCoV)
CureVac, CEPI
Germany RNA (unmodified RNA)[291] Phase III (39,020)[292][293]
Phase 2b/3 (36,500): Multicenter efficacy and safety trial in adults.
Phase 3 (2,520): Randomized, observer-blinded, placebo-controlled.
Nov 2020 – Jun 2021, Argentina, Belgium, Colombia, Dominican Republic, France, Germany, Mexico, Netherlands, Panama, Peru, Spain
Phase I–II (944)[294][295]
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 (1)
SOBERANA 02 (FINLAY-FR-2)
Instituto Finlay de Vacunas
Cuba Subunit (conjugate) Phase III (44,010)[296][297]
Multicenter, adaptive, parallel-group, randomized, placebo-controlled, double-blind
Mar – Nov 2021, Cuba
Phase I–II (950)[298][299]
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)
CIGB-66 (ABDALA)
Center for Genetic Engineering and Biotechnology
Cuba Subunit Phase III (48,000)[301]
Multicenter, randomized, double-blind, placebo-controlled.
Mar  – Jul 2021, Cuba
Phase I–II (132)[302]
Randomized, double-blind, placebo-controlled, factorial.
Nov 2020  – May 2021, Cuba
Chinese Academy of Medical Sciences COVID-19 vaccine[303][304]
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
QazCovid-in[305]
Research Institute for Biological Safety Problems
Kazakhstan Inactivated SARS‑CoV‑2 Phase III (3,000)
Randomised, blind, placebo-controlled trial[306]
Dec 2020 – Mar 2021, Kazakhstan [306]
Phase I–II (244[307])
Sep  – Nov 2020, Kazakhstan
ZyCoV-D[124]
Cadila Healthcare
India DNA (plasmid expressing SARS‑CoV‑2 S protein) Phase III (28,216)[308][309]
Randomised, blind, placebo-controlled trial[310]
Jan 2021 – ?, India[311]
Phase I–II (1,000)
Interventional; randomized, double-blind, placebo-controlled[312][310]
Jul 2020 – Jan 2021, India
CoVLP[313]
Medicago, GSK
Canada, United Kingdom Virus-like particles[g] (recombinant, plant-based with AS03) Phase II–III (30,918)
Event-driven, randomized, observer blinded, placebo-controlled[315]
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[316]
Emergency (1)
SCB-2019[318][319]
Clover Biopharmaceuticals,[320][321] 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
COVIran Barakat[322]
Barakat Pharmaceutical Group, Shifa Pharmed Industrial Group
Iran Inactivated SARS‑CoV‑2 Phase II–III (20,000)
Randomized, double-blind, parallel arms, placebo-controlled.[323]
Mar  – May 2021, Iran
Phase I (56)
Randomized, double-blind, parallel arms, placebo-control.[324]
Dec 2020 – Feb 2021, Iran
UB-612
United Biomedical,Inc, COVAXX, DASA
Brazil, United States Subunit Phase II–III (11,170)[325][326]
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)[327]
Open-label study
Sep 2020–Jan 2021, Taiwan
GRAd-COV2[328][329]
ReiThera, Lazzaro Spallanzani National Institute for Infectious Diseases
Italy Adenovirus vector (modified gorilla adenovirus vector, GRAd) Phase II–III (10,300)[330][331]
Randomized, stratified, observer-blind, placebo-controlled.
Mar–May 2021, Italy
Phase I (90)[332]
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)[333][334]
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)[335]
Single-center, Randomized, Placebo-controlled, Double-blind.
Aug –Oct 2020, China
MVC-COV1901
Medigen Vaccine Biologics
Taiwan Subunit Phase II (4,100)[336][337]
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)[338]
Prospective, open-labeled, single-center
Oct 2020–Jan 2021, Taiwan
Minhai COVID-19 vaccine
Minhai Biotechnology Co.
China Inactivated SARS‑CoV‑2 (vero cell) Phase II (1,000)[339]
Randomized, double-blind, placebo parallel-controlled.
Oct 2020 – Jun 2021, China
Phase I (180)[340]
Randomized, double-blind, placebo parallel-controlled.
Oct 2020 – Jun 2021, China
DelNS1-2019-nCoV-RBD-OPT
Beijing Wantai Biological Pharmacy
China Viral vector Phase II (720)[341]
Nov 2020 – Dec 2021, China
Phase I (60)[342]
Sep 2020 – Oct 2021, China
Nanocovax[343]
Nanogen Pharmaceutical Biotechnology JSC
Vietnam Subunit (SARS‑CoV‑2 recombinant spike protein with aluminum adjuvant)[344][345] Phase II (560)[346]
Randomization, double-blind, multicenter, placebo-controlled
Feb – May 2021, Vietnam
Phase I (60)[343]
Open label, dose escalation
Dec 2020 – Jan 2021, Vietnam
Walvax COVID-19 vaccine (ARCoV)[347]
PLA Academy of Military Science, Walvax Biotech[348]
China RNA Phase II (420)
Jan 2021 – Mar 2022, China[349]
Phase I (168)
Jun 2020 – Dec 2021, China
ERUCOV-VAC
Health Institutes of Turkey
Turkey Inactivated SARS‑CoV‑2 Phase II (250)[350]
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)[351]
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[125][126]
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.[352]
Phase IIa (640): Randomized, double-blinded, placebo-controlled, dose-finding.[353]
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.[354]
April 2020 – Feb 2022, United States, South Korea (phase Ib-IIa)
AG0302-COVID‑19[127][355]
AnGes Inc.,[356] AMED
Japan DNA vaccine (plasmid) Phase II–III (500)
Randomized, double-blind, placebo controlled[357]
Nov 2020 – May 2021, Japan
Phase I–II (30)
Randomized/non-randomized, single-center, two doses
Jun  – Nov 2020, Osaka
IIBR-100 (Brilife)[132]
The Israel Institute for Biological Research
Israel Vesicular stomatitis vector (recombinant) Phase I–II (1,040)[358]
Oct 2020 – May 2021, Israel
Preclinical
ARCT-021 (Lunar-COV19)[359][360]
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[361]
Phase IIb (600): Randomized, observer-blind, placebo-controlled[362]
Aug 2020 – Apr 2022, Singapore, United States (phase IIb)
Preclinical
VBI-2902[363]
Variation Biotechnologies
United States Virus-like particle Phase I–II (780)[364]
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)[365]
Randomized, placebo-controlled, observer-blind.
Mar 2021 – Apr 2022; Brazil, Mexico, Thailand, Vietnam[366]
Preclinical
Sanofi–Translate Bio COVID-19 vaccine (MRT5500)[367]
Sanofi Pasteur and Translate Bio
France, United States RNA Phase I–II (415)[368]
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
EuCorVac-19[369]
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)[370]
Randomized, placebo-controlled, multi-center.
Aug 2020 – 2021, Australia
Preclinical
GX-19 (GX-19N)[128][371][129]
Genexine consortium,[372] 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)[373][374]
Adaptive.
Dec 2020 – Jul 2021, Indonesia (phase I), United States (phase I/II)
Preclinical
VLA2001[117][118]
Valneva
France Inactivated SARS‑CoV‑2 Phase I–II (150)
Randomized, multi-center, double-blinded
Dec 2020 – Feb 2021, United Kingdom
Preclinical
TAK-919[375]
Takeda
Japan RNA Phase I–II (200)[376]
Randomized, observer-blind, placebo-controlled
Jan 2021 – Mar 2022, Japan
Preclinical
TAK-019[377]
Takeda
Japan Subunit Phase I–II (200)[378]
Randomized, observer-blind, placebo-controlled.
Feb 2021 – April 2022, Japan
Preclinical
COVID-eVax
Takis Biotech
Italy DNA Phase I–II (160)[379]
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)[380]
Dose-finding Study.
Jan  – Mar 2021, Thailand
Preclinical
COVID‑19/aAPC[130]
Shenzhen Genoimmune Medical Institute[381]
China Lentiviral vector (with minigene modifying aAPCs) Phase I (100)
Mar 2020 – Jul 2023, Shenzhen
Preclinical
LV-SMENP-DC[131]
Shenzhen Genoimmune Medical Institute[381]
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 (160)[382][383][384]
Open-Label.
Oct 2020  – Apr 2022, South Africa, United States
Preclinical
COVAX-19[385]
Vaxine Pty Ltd[386]
Australia Subunit (recombinant protein) Phase I (40)
Jun 2020 – Jul 2021, Adelaide
Preclinical
HGC019[387]
Gennova Biopharmaceuticals, HDT Biotech Corporation[388]
India, United States RNA Phase I (120)[389]
Jan 2021 – ?, India
Preclinical
Bio E COVID-19 (BECOV2D)[390][391]
Biological E. Limited, Baylor College of Medicine,[392] CEPI
India, United States Subunit (using an antigen) Phase I–II (360)[393]
Randomized, Parallel Group Trial
Nov 2020 – Feb 2021, India
Preclinical
Bangavax [394][395]
Globe Biotech Ltd. of Bangladesh
Bangladesh RNA Phase I (100)[394][396]
Randomized, Parallel Group Trial
Feb 2021 – Feb 2022,[397] Bangladesh
Preclinical
PTX-COVID19-B[398]
Providence Therapeutics
Canada RNA Phase I (60)[398]
Jan  – May 2021, Canada
Preclinical
COVAC-2[399]
VIDO (University of Saskatchewan)
Canada Subunit Phase I (108)[399]
Feb 2021 – Jan 2022, Halifax
Preclinical
COVI-VAC
Codagenix Inc.
United States Attenuated Phase I (48)[400]
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)[401]
Open-label, dose escalation, non-randomized
Feb  – Jun 2021, United States
Preclinical
COVIGEN
University of Sydney
Australia DNA Phase I (150)[402]
Double-blind, dose-ranging, randomised, placebo-controlled.
Feb 2021 – Jun 2022, Sydney
Preclinical
BBV154[403]
Bharat Biotech[404]
India Adenovirus vector (intranasal) Phase I (175)[403]
Randomized, double-blinded, multicenter.
Mar 2021, India
Preclinical
MV-014-212[405]
Meissa Vaccine Inc.
United States Attenuated Phase I (130)[406]
Randomized, double-blinded, multicenter.
Mar 2021 – Oct 2022, United States
Preclinical
S-268019
Shionogi
Japan Subunit Phase I–II (214)[407]
Randomized, double-blind, placebo-controlled, parallel-group.
Dec 2020 – Jun 2022, Japan
Preclinical
GBP510
SK Bioscience Co. Ltd.
South Korea Subunit Phase I–II (260)[408]
Placebo-controlled, randomized, observer-blinded, dose-finding.
Jan  – Aug 2021, South Korea
Preclinical
KBP-201
Kentucky Bioprocessing
United States Subunit Phase I–II (180)[409]
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)[410]
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)[411]
Randomized, single center, open-label, dose-finding.
Aug  – Nov 2020, Taiwan
Preclinical
AKS-452
University Medical Center Groningen
Netherlands Subunit Phase I–II (130)[412]
Non-randomized, Single-center, open-label, combinatorial.
Jan  – Apr 2021, Netherlands
Preclinical
GLS-5310
GeneOne Life Science Inc.
South Korea DNA Phase I–II (345)[413]
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)[414]
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)[415]
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)[416]
Randomized, double blind, controlled trial with factorial design.
Mar  – Apr 2021, Iran
Preclinical
NBP2001
SK Bioscience Co. Ltd.
South Korea DNA Phase I (50)[417]
Placebo-controlled, Randomized, Observer-blinded, Dose-escalation.
Dec 2020  – Apr 2021, South Korea
Preclinical
CoVac-1
University Hospital Tuebingen
Germany Subunit Phase I (36)[418]
Placebo-controlled, Randomized, Observer-blinded, Dose-escalation.
Nov 2020  – Sep 2021, Germany
Preclinical
bacTRL-Spike
Symvivo
Canada DNA Phase I (24)[419]
Randomized, observer-blind, placebo-controlled.
Nov 2020  – Feb 2022, Australia
Preclinical
Razi Cov Pars
Razi Vaccine and Serum Research Institute
Iran Subunit Phase I (133)[420]
Randomized, double blind, placebo controlled.
Jan  – Mar 2021, Iran
Preclinical
CORVax12
Providence Health & Services
United States DNA Phase I (36)[421]
Open-label.
Dec 2020  – May 2021, United States
Preclinical
ChAdV68-S (SAM-LNP-S)
NIAID, Gritstone Oncology
United States Viral vector Phase I (130)[422]
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)[423]
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)[424]
Double-blind, randomized, placebo-controlled, first-in-Human.
Sep  – Dec 2020, United States
Preclinical
AdCLD-CoV19
Cellid Co
South Korea Viral vector Phase I–II (150)[410]
Phase I: Dose Escalation, Single Center, Open.
Phase IIa: Multicenter, Randomized, Open.
Dec 2020 – Mar 2021, South Korea
Preclinical
SpFN COVID-19 Vaccine
United States Army Medical Research and Development Command
United States Subunit Phase I (72)[425]
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)[426]
Open, Single-center.
Oct 2020 – May 2021, Germany
Preclinical
COVIVAC[427]
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.[428] Phase I (120)[429]
Mar  – Jul 2021, Vietnam
Preclinical
ReCOV
Jiangsu Rec-Biotechnology Co Ltd
China Subunit Phase I (160)[430]
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)[431]
Randomized, double-blinded, placebo-controlled, dose-escalation, and dose-expansion.
Mar 2021 – Sep 2022, Hong Kong
Preclinical
SARS-CoV-2 VLP Vaccine
Scientific and Technological Research Council of Turkey
Turkey Virus-like particle Phase I (36)[432]
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)[433]
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
LNP-nCoVsaRNA[434]
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
?
COVID-19-101
Institut Pasteur
France Viral vector Terminated (90)[435]
Randomized, Placebo-controlled.
Aug  – Nov 2020, Belgium, France
?
SARS-CoV-2 Sclamp/V451[122][123]
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[436] and V591/MV-SARS-CoV-2[437] Merck & Co. (Themis BIOscience), Institut Pasteur, University of Pittsburgh's Center for Vaccine Research (CVR), CEPI United States, France Vesicular stomatitis virus vector[438] / Measles virus vector[439] 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.[440]
  1. ^ Serum Institute of India will be producing the ChAdOx1 nCoV-19 vaccine for India[187] and other low- and middle-income countries.[188]
  2. ^ Oxford name: ChAdOx1 nCoV-19. Manufacturing in Brazil to be carried out by Oswaldo Cruz Foundation.[189]
  3. ^ a b Recommended interval. The second dose of the Pfizer–BioNTech and Moderna vaccines can be administered up to 6 weeks after the first dose to alleviate a shortage of supplies.[196][197]
  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.[198][199]
  5. ^ Storage temperature for the frozen Gam-COVID-Vac formulation. The lyophilised Gam-COVID-Vac-Lyo formulation can be stored at 2-8°C.[206]
  6. ^ Latest Phase with published results.
  7. ^ Virus-like particles grown in Nicotiana benthamiana[314]
  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.[441] 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.[441][442] 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.[442] 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.[442] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines.[441][442]

Deployment

Location Vaccinated[b] % of pop.[c]
  World[d] 419,975,023 5.4%
 China[e] 161,121,000 --
 United States 114,436,039 34.2%
 India 85,763,852 6.2%
 EU 64,904,789 14.6%
 United Kingdom 31,903,366 47.0%
 Brazil 19,886,870 9.4%
 Germany 12,204,176 14.6%
 Mexico[e] 10,984,869 --
 Turkey 10,777,451 12.8%
 France 10,148,039 14.9%
 Indonesia 9,374,089 3.4%
 United Arab Emirates[e] 8,923,543 --
 Italy 8,697,556 14.4%
 Russia 8,333,331 5.7%
 Chile 7,284,213 38.1%
 Spain 7,159,716 15.3%
 Canada 6,989,688 18.4%
 Saudi Arabia[e] 5,982,107 --
 Bangladesh 5,568,703 3.4%
 Israel 5,307,975 61.3%
 Poland 5,167,241 13.7%
 Morocco 4,449,047 12.1%
 Argentina 4,244,964 9.4%
 Hungary 2,760,938 28.6%
 Romania 2,206,254 11.5%
 Colombia 2,172,751 4.3%
 Netherlands 2,057,562 12.0%
 Serbia 1,716,843 25.2%
 Belgium 1,677,523 14.5%
 Nepal[e] 1,600,000 --
 Portugal 1,504,553 14.8%
 Austria 1,397,538 15.5%
 Greece 1,394,013 13.4%
 Sweden 1,355,828 13.4%
 Czech Republic 1,344,526 12.6%
 South Korea 1,148,060 2.2%
 Singapore 1,131,658 19.3%
 Pakistan 1,114,000 0.5%
 Japan 1,101,698 0.9%
 Australia[e] 1,077,511 --
 Finland 1,066,860 19.3%
 Switzerland 1,048,063 12.1%
 Qatar[e] 1,041,632 --
 Dominican Republic 1,000,000 9.2%
 Nigeria 964,387 0.5%
 Sri Lanka 925,082 4.3%
 Cambodia 913,171 5.5%
 Philippines 872,213 0.8%
 Norway 835,970 15.4%
 Denmark 835,271 14.4%
 Slovakia 811,508 14.9%
 Uruguay 808,486 23.3%
 Ireland 716,636 14.6%
 Azerbaijan 672,503 6.6%
 Ghana 647,380 2.1%
 Peru 625,762 1.9%
 Kuwait[e] 604,861 --
 Mongolia[e] 599,132 --
 Bahrain 557,298 32.8%
 Malaysia 546,762 1.7%
 Hong Kong 543,110 7.2%
 Panama[e] 478,146 --
 Bhutan 473,393 61.4%
 Thailand 470,301 0.7%
 Lithuania 463,596 17.0%
 Bulgaria 454,711 6.5%
 Croatia 440,890 10.7%
 Jordan 404,912 4.0%
 Myanmar 380,000 0.7%
 Ukraine 373,000 0.9%
 Rwanda 348,926 2.7%
 Kenya 340,121 0.6%
 Senegal 326,910 2.0%
 Slovenia 308,522 14.8%
 Costa Rica 291,368 5.7%
 South Africa 288,368 0.5%
 Bolivia 282,801 2.4%
 Maldives 265,235 49.1%
 Ecuador 244,159 1.4%
 Albania[e] 242,542 --
 Estonia 236,598 17.8%
 Angola 181,578 0.6%
 El Salvador 180,000 2.8%
 Lebanon 170,506 2.5%
 Malta 167,130 37.9%
 Malawi 164,733 0.9%
 Zimbabwe 153,238 1.0%
 Oman 152,036 3.0%
 Latvia 149,157 7.9%
 Egypt[e] 148,987 --
 Uganda 144,025 0.3%
 Palestine 131,394 2.6%
 Guatemala 130,985 0.7%
 Iran 124,193 0.2%
 Cyprus 124,165 14.2%
 Afghanistan 120,000 0.3%
 Tunisia 119,919 1.0%
 Iraq 103,006 0.3%
 Venezuela 98,000 0.3%
 Luxembourg 91,074 14.6%
 Kazakhstan 90,748 0.5%
 Algeria[e] 75,000 --
 New Zealand 71,013 1.5%
 Guinea[e] 67,863 --
 Seychelles 64,508 65.6%
 Sudan 63,837 0.2%
 Barbados 63,738 22.2%
 Iceland 58,567 17.2%
 Vietnam 58,037 0.1%
 Moldova 57,561 1.4%
 Mozambique 57,305 0.2%
 Northern Cyprus 53,886 14.1%
 Ivory Coast 53,071 0.2%
 Honduras 52,772 0.5%
 Paraguay 46,000 0.6%
 Jersey 44,981 44.5%
 Isle of Man 44,343 52.2%
 Macau 42,802 6.6%
 Togo 42,092 0.5%
 Jamaica 41,901 1.4%
 Laos 40,732 0.6%
 Belarus 40,518 0.4%
 Guyana 40,468 5.1%
 Uzbekistan 35,000 0.1%
 Montenegro 34,172 5.4%
 Gibraltar 32,895 97.6%
 Suriname 32,614 5.6%
 Sierra Leone 31,889 0.4%
 Cayman Islands 31,661 48.2%
 Guernsey 29,575 44.1%
 Antigua and Barbuda 26,424 27.0%
 Bermuda 23,791 38.2%
 Saint Lucia[e] 23,150 --
 Belize 22,067 5.6%
 North Macedonia 21,333 1.0%
 Eswatini 20,262 1.8%
 Taiwan 20,075 0.1%
 Dominica 17,775 24.7%
 Georgia 15,693 0.4%
 Botswana 12,945 0.6%
 Turks and Caicos Islands 12,935 33.4%
 Gambia 12,674 0.5%
 Andorra[e] 12,440 --
 Monaco 11,715 29.9%
 Equatorial Guinea 11,090 0.8%
 Saint Vincent and the Grenadines[e] 10,519 --
 Grenada 9,821 8.7%
 São Tomé and Príncipe 9,724 4.4%
 San Marino 9,021 26.6%
 Saint Kitts and Nevis 8,573 16.1%
 Faroe Islands 7,345 15.0%
 Bahamas 7,000 1.8%
 Liechtenstein[e] 6,914 --
 Anguilla 5,348 35.7%
 Trinidad and Tobago 4,777 0.3%
 Greenland 3,927 6.9%
 Mauritius 3,843 0.3%
 Saint Helena 3,107 51.2%
 Falkland Islands 2,605 74.8%
 Namibia 2,526 0.1%
 Syria 2,500 0.0%
 Kosovo 2,500 0.1%
 Gabon 2,433 0.1%
 Cape Verde 2,184 0.4%
 Solomon Islands 2,000 0.3%
 Mauritania 1,366 0.0%
 Montserrat 1,112 22.2%
 Kyrgyzstan 849 0.0%
 Mali 643 0.0%
 Armenia 565 0.0%
 Brunei 340 0.1%
 Papua New Guinea 250 0.0%
 F.S. Micronesia[444] 16,402 15.8%
 Marshall Islands[444] 13,205 22.6%
 Palau[444] 8,468 47.3%
 Vatican City[445][446] 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. ^ Percentage of population that has received at least one dose of a COVID-19 vaccine.
  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 n o p q r This country's data reflects total doses administered, not the first shot only.

As of 9 April 2021, 754.3 million COVID‑19 vaccine doses had been administered worldwide based on official reports from national health agencies collated by Our World in Data.[447]

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).[448] Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country.[449][450][451][452] Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need.[449][450][452] 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.[453] 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.[452]

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."[454] 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.[448][455][456][457] 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.[458][459] 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.[454][456][458]

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".[460] The declaration is effective in the United States through 1 October 2024.[460]

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.[461] 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.[462]

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).[463][464]

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.[465]

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."[466]

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.[467][468][469]

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.[470]

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."[471] 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.[472]

On 10 March 2021, the United States, Britain, European Union nations and other WTO members, blocked a push by over 80 developing countries to waive COVID‑19 vaccine patent rights in an effort to boost production of vaccines for poor nations.[473]

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[474] – 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.[475] As of March 2021, 19% of US adults claim to have been vaccinated and 50% of US adults plan to get vaccinated.[476][477]

In an effort to demonstrate the vaccine's safety, prominent politicians have received it on camera, with others pledging to do so.[478][479][480]

Vaccine selfies

Many folks are taking vaccine selfies and the photos have gone viral.[481]

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.[482]

Politicians and heads of state

Several heads of state and government ministers have released photographs of their vaccinations, encouraging others to be vaccinated including Kyriakos Mitsotakis, Zdravko Marić, Olivier Véran, US President Joe Biden, Former US Presidents Barack Obama, George W. Bush and Bill Clinton, the Dalai Lama, Alexandria Ocasio-Cortez, Nancy Pelosi and Kamala Harris.[483][484][483]

Elizabeth II and Prince Philip announced they had the vaccine, breaking from protocol of keeping the British royal family's health private.[482] Pope Francis and Pope Emeritus Benedict both announced they had been vaccinated.[482]

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".[482] 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.[483] 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."[483]

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, Buzz Aldrin and Patrick Stewart have released photographs of themselves getting vaccinated and encouraging others to do the same.[482][483] Dame Judi Dench and Joan Collins announced they have been vaccinated.[482]

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.[482][483] 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."[482] Sir David Attenborough announced that he has been vaccinated.[482]

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."[483]

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'.[485]

Oprah Winfrey and Whoopi Goldberg have spoken about being vaccinated for COVID‑19 and encouraged black Americans to be vaccinated.[483] 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."[483]

See also

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