COVID-19 vaccine


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 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]

COVID-19 vaccination doses administered per 100 people, as of 15 February 2021
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

As of February 2021, 66 vaccine candidates are in clinical research, including 17 in Phase I trials, 23 in Phase I–II trials, 6 in Phase II trials, and 20 in Phase III trials.[3] Trials for four other candidates were terminated.[3] In Phase III trials, several COVID‑19 vaccines demonstrate efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of February 2021, eleven vaccines are authorized by at least one national regulatory authority for public use: two RNA vaccines (the Pfizer–BioNTech vaccine and the Moderna vaccine), four conventional inactivated vaccines (BBIBP-CorV, Covaxin, CoronaVac, and CoviVac), four viral vector vaccines (Sputnik V, the Oxford–AstraZeneca vaccine, Convidicea, and the Johnson & Johnson vaccine), and one peptide vaccine (EpiVacCorona).[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] As of 27 February 2021, 239.60 million doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies.[5] Pfizer, Moderna, and AstraZeneca predicted a manufacturing capacity of 5.3 billion doses in 2021, which could be used to vaccinate about 3 billion people (as the vaccines require two doses for a protective effect against COVID‑19). By December 2020, more than 10 billion vaccine doses had been preordered by countries,[6] with about half of the doses purchased by high-income countries comprising 14% of the world's population.[7]

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.[8] 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.[9] 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[10] and MERS[11] 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.[12][13][14] As of 2020, there is no cure or protective vaccine proven to be safe and effective against SARS in humans.[15][16] There is also no proven vaccine against MERS.[17] 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.[15][18] As of March 2020, there was one (DNA based) MERS vaccine which completed Phase I clinical trials in humans[19] and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).[20]

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.[21] Multiple steps along the entire development path are evaluated, including 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.[8][22] 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.[21][23] As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020,[24] 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.[21][25]

Planning and development


Since early 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[26] 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.[26][27]

There have been several unique challenges with COVID-19 vaccine development. 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.[27][28][29] Additionally, research at universities is obstructed by physical distancing and closing of laboratories.[30][31]

Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels and adverse effects of the candidate vaccine.[32][33] 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;[34] clinical trial organizers may encounter people unwilling to be vaccinated due to vaccine hesitancy[35] or disbelieving the science of the vaccine technology and its ability to prevent infection.[36] 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.[37][38][39]

Organizations

Internationally, the Access to COVID-19 Tools Accelerator is a G20 and World Health Organization (WHO) initiative announced in April 2020.[40][41] 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.[42] 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.[43]

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,[44] and to support clinical trials and develop manufacturing and supply chains for vaccines.[45] 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.[23] Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing.[46] 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.[47] 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.[23][48] In May 2020, the government announced funding for a fast-track program called Operation Warp Speed.[49][50]

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.[23][21]

History

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

After a coronavirus was isolated in December 2019,[51] 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.[52][53][54] Since early 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[55] 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.[53][56][57][58] 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.[52][55]

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.[59] 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,[60] with four vaccine candidates entering human evaluation in March (see the table of clinical trials started in 2020, below).[52][61]

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.[62] 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.[63]

The Pfizer-BioNTech partnership submitted an EUA request to the FDA for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020.[64][65] On 2 December 2020, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine,[66][67] 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.[68][69][70] As of 21 December, many countries and the European Union[71] 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.[72][73] 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.[74] A week later, they granted an EUA for mRNA-1273, the Moderna vaccine.[75][76][77]

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][78] 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.[78] 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.[8][78][27][28]

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.[78][27][28] 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.[78][27]

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.[79][80][81][82]

RNA vaccines were the first COVID-19 vaccines to be authorized in the United States and the European Union.[83][84] As of January 2021, authorized vaccines of this type are the Pfizer-BioNTech COVID‑19 vaccine[85][86][87] and the Moderna COVID-19 vaccine.[88][89] As of February 2021, the CVnCoV RNA vaccine from CureVac is awaiting authorization in the EU.[90]

Adenovirus vector vaccines

These vaccines are examples of non-replicating viral vectors, using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein.[91] 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.[91]

As of January 2021, authorized vaccines of this type are the British Oxford–AstraZeneca COVID-19 vaccine,[92][93][94] Russian Sputnik V,[95] Chinese Convidicea, and the Johnson & Johnson COVID-19 vaccine.[96][97]

Convidicia and Johnson & Johnson's vaccine's are both one-shot vaccines which offer less complicated logistics; and can be stored under ordinary refrigeration for several months.[98][99]

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.[100]

As of January 2021, authorized vaccines of this type are the Chinese CoronaVac[101][102][103] and BBIBP-CorV[104] as well as the Indian Covaxin. Vaccines in clinical trials include the Valneva COVID-19 vaccine.[105][106]

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.[107]

As of January 2021, the only authorized vaccine of this type is the peptide vaccine EpiVacCorona.[108] Vaccines in clinical trials include the Novavax COVID-19 vaccine[109] and RBD-Dimer.[3] 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.[110][111]

Other types

Additional types of vaccines that are in clinical trials include multiple DNA plasmid vaccines,[112][113][114][115][116][117] at least two lentivirus vector vaccines,[118][119] a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.[120]

Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID‑19 infection.[121] 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.[122]

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.[32][33] A Phase I–II trial consists of preliminary safety and immunogenicity testing, is typically randomized, placebo-controlled, while determining more precise, effective doses.[33] 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.[32][33] 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.[34][123][124]

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.[125][126] 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.[125][127]

List of authorized and approved vaccines

National regulatory authorities have granted emergency use authorizations for eleven 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 Technology Current phase (participants) Completed phase[lower-alpha 1] (participants) Authorization
BBIBP-CorV[104]
Sinopharm: Beijing Institute of Biological Products, Wuhan Institute of Biological Products
China Inactivated SARS‑CoV‑2 vaccine (vero cells) Phase III (48,000)
Randomized, double-blind, parallel placebo-controlled, to evaluate safety and protective efficacy.
Sinopharm's internal analysis indicated a 79% efficacy.[128]
Jul 2020  Jul 2021, United Arab Emirates, Bahrain, Jordan,[129] Argentina,[130] Morocco,[131] Peru[132]
Phase I–II (320)
Neutralizing antibodies at day 14 after two injections[133]
Apr 2020  Jun 2020, China
Emergency (17)
Full (4)
Sputnik V COVID-19 vaccine
Gamaleya Research Institute of Epidemiology and Microbiology
Russia Adenovirus vector vaccine (recombinant adenovirus type 5 and 26 vector) Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety.[156]
Interim analysis from the trial was published in The Lancet, indicating 91.6% efficacy without unusual side effects.[157]
Aug 2020  May 2021, Russia, Belarus,[158] India,[159][160] Venezuela,[161][162] UAE[163]
Phase I–II (76)
Neutralizing antibody and T cell responses.[164]
Jun 2020[164]  Sep 2020, Russia
Emergency (34)
Full (5)
Pfizer–BioNTech COVID-19 vaccine (Comirnaty)[85][86][87]
BioNTech, Pfizer
United States, Germany RNA vaccine (modRNA encapsulated in lipid nanoparticles) Phase III (43,448)
Randomized, placebo-controlled.
Positive results from an interim analysis were announced on 18 November 2020[203] and published on 10 December 2020 reporting an overall efficacy of 95%.[204][205]
Jul 2020  Nov 2020,[206][207] Germany, United States
Phase I–II (45)
Strong RBD-binding IgG and neutralizing antibody response peaked 7 days after a booster dose, robust CD4+ and CD8+ T cell responses, undetermined durability.[208]
May 2020  ?
Emergency (37)
Full (11)
Moderna COVID-19 vaccine[88][89]
Moderna, NIAID, BARDA, CEPI
United States RNA vaccine (modRNA encapsulated in lipid nanoparticles) 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[269] and published on 30 December 2020 reporting an overall efficacy of 94%.[270]
Jul 2020  Oct 2022, United States
Phase I–II (720)[271][272]
Dose-dependent neutralizing antibody response on two-dose schedule; undetermined durability.[273][274][275]
Mar 2020  Nov 2021, United States
Emergency (10)
Full (5)
Oxford–AstraZeneca COVID-19 vaccine (Covishield)[lower-alpha 3][lower-alpha 4][92][93][94]
University of Oxford, AstraZeneca, CEPI
United Kingdom Adenovirus vector vaccine (modified chimpanzee adenovirus vector, ChAdOx1) Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity.[296]
Positive results from an interim analysis of four ongoing trials were announced on 23 November 2020, and published on 8 December 2020. Overall efficacy was 70%, ranging from 62% to 90% with different dosing regimens, with a peer-reviewed safety profile.[297]
May 2020  Aug 2021, Brazil (5,000),[298] United Kingdom, India[299]
Phase I–II (543)
Spike-specific antibodies at day 28; neutralizing antibodies after a booster dose at day 56.[300]
Emergency (30)
Full (4)
CoronaVac[101][102][103]
Sinovac
China Inactivated SARS‑CoV‑2 vaccine Phase III (33,620)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
Positive results from an interim analysis of a small sample were announced by Turkey on 24 December 2020, with an efficacy of 91%.[340] Additional results were announced by Indonesia on 11 January, with an overall efficacy of 65%.[341] The vaccine was 50% effective at preventing symptomatic infections in a Brazilian trial.[342]
Jul 2020  Oct 2021, Brazil (15,000);[343] Aug 2020 – January 2021, Indonesia (1,620); Chile (3,000);[344] Turkey (13,000)[345]
Phase II (600)
Immunogenicity eliciting 92% seroconversion at lower dose and 98% at higher dose after 14 days[346]
May 2020  July 2020, China
Emergency (15)
Full (1)
Johnson & Johnson COVID-19 vaccine[96][97]
Janssen Pharmaceutica (Johnson & Johnson), BIDMC
Netherlands, United States Adenovirus vector vaccine (adenovirus serotype 26) Phase III (40,000)
Randomized, double-blinded, placebo-controlled
Positive results from an interim analysis were announced on 29 January 2021.[360]
Jul 2020  2023, United States, Argentina, Brazil, Chile, Colombia, Mexico, Peru, the Philippines, South Africa, Ukraine
Phase I–II (1,045)
Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose and reached 100% by day 57 with a further increase in titers, regardless of vaccine dose or age group. Titers remained stable until at least day 71.[361]
Emergency (5)
Full (0)
  • None
Ad5-nCoV (Convidicea)
CanSino Biologics, Beijing Institute of Biotechnology of the Academy of Military Medical Sciences
China Adenovirus vector vaccine (recombinant adenovirus type 5 vector) 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.[367]
Mar–Dec 2020, China; Sep 2020  Dec 2021, Pakistan; Sep 2020  Nov 2020, Russia,[368] China, Argentina, Chile;[369] Mexico;[370] Pakistan;[371] Saudi Arabia[372][373]

Phase II (508)
Neutralizing antibody and T cell responses[374]
Emergency (3)
Full (0)
  • None
EpiVacCorona[108]
Vector Institute
Russia Peptide vaccine[108] Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety
Nov 2020  Dec 2021, Russia[378]
Phase I–II (100)
Simple, blind, placebo-controlled, randomized study of safety, reactogenicity and immunogenicity[108]
Jul 2020[108]  Sep 2020,[379] Russia
Emergency (1)
Full (1)
BBV152 (Covaxin)
Bharat Biotech, Indian Council of Medical Research
India Inactivated SARS‑CoV‑2 vaccine Phase III (25,800)
Randomised, observer-blinded, placebo-controlled[384]
Nov 2020  Mar 2021, India[385]
Phase I (375)
Dose-dependent neutralizing antibody response on two-dose schedule. Pending Phase II reports.[386]
Emergency (1)
Full (0)
  • None
CoviVac[387]
The Chumakov Centre at the Russian Academy of Sciences
Russia Inactivated SARS‑CoV‑2 vaccine Phase III (3,000)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety.
Phase I–II (300)
Simple, blind, placebo-controlled, randomized study of safety, reactogenicity and immunogenicity[388]
Oct 2020[389]  Dec 2020, Russia
Emergency (1)
Full (0)
  • None

Vaccine candidates in human trials

COVID‑19 candidate vaccines in Phase IIII trials[3][391][392]
Vaccine candidates,
developers, and sponsors
Country of origin Technology Current phase (participants)
design
Completed phase[lower-alpha 5] (participants)
Immune response
Pending authorization
Novavax COVID-19 vaccine[109]
Novavax, CEPI
United States Subunit vaccine (SARS‑CoV‑2 recombinant spike protein nanoparticle with adjuvant) Phase III (45,000)
Randomised, observer-blinded, placebo-controlled trial[393]
Sep 2020  Jan 2021, UK (15,000); December 2020  Mar 2021, US, Mexico, (30,000)[394]
Phase I–II (131)
IgG and neutralizing antibody response with adjuvant after booster dose.[395]
Emergency (1)
ZF2001 (RBD-Dimer)[3]
Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.
China Subunit vaccine (recombinant) Phase III (29,000)
Randomized, double-blind, placebo-controlled[398]
Dec 2020  Apr 2022, China, Ecuador, Indonesia, Malaysia, Pakistan, Uzbekistan[399][400]
Phase II (900)
Interventional; randomized, double-blind, placebo-controlled[401]
Jun 2020  Sep 2021, Chongqing
CureVac COVID-19 vaccine (CVnCoV)
CureVac, CEPI
Germany RNA vaccine (unmodified RNA)[402] Phase III (36,500)[403]
Phase 2b/3: Multicenter efficacy and safety trial in adults
Nov 2020  ?, Argentina, Belgium, Colombia, Dominican Republic, France, Germany, Mexico, Netherlands, Panama, Peru, Spain
Phase I–II (944)[404][405]
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)
ZyCoV-D[112]
Cadila Healthcare
India DNA vaccine (plasmid expressing SARS‑CoV‑2 S protein) Phase III (26,000)[406]
Jan 2021  ?, India[407]
Phase I–II (1,000)
Interventional; randomized, double-blind, placebo-controlled[408][409]
Jul 2020  Jan 2021, India
CoVLP[410]
Medicago, GSK
Canada, United Kingdom Virus-like particles[lower-alpha 6] (recombinant, plant-based with AS03) Phase II–III (30,612)
Event-driven, randomized, observer blinded, placebo-controlled[412]
Nov 2020  Apr 2022, 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.
IIBR-100 (Brilife)[120]
The Israel Institute for Biological research
Israel Vesicular stomatitis vector vaccine (recombinant) Phase II (1,000)[413]
Dec 2020  spring 2021, Israel
Phase I (80)[120]
Subjects (18–55 years old) randomly receiving a single administration of IIBR-100 at the low, mid, or high dose, or saline, or two administrations at a low dose, or saline, 28 days apart.
Oct–Nov 2020, Israel
FINLAY-FR-2 (SOBERANA 02)
Instituto Finlay de Vacunas
Cuba Conjugate vaccine Phase II (910)[414]
Allocation: Randomized controlled trial. Masking: Double Blind. Control group: Placebo. Study design: Parallel.
Jan–Mar 2021, Cuba
Phase I (40)[415]
Allocation: Non-randomized controlled trial. Masking: Open. Control group: Uncontrolled. Study design: Adaptive, sequential
Nov 2020  Jan 2021, Cuba
Nano Covax[416]
Nanogen Pharmaceutical Biotechnology JSC
Vietnam Subunit vaccine (SARS‑CoV‑2 recombinant spike protein with aluminum adjuvant)[417][418] Phase II (560)[419]
Randomization, double-blind, multicenter, placebo-controlled
Feb  May 2021, Vietnam
Phase I (60)[416]
Open label, dose escalation
Dec 2020  Jan 2021, Vietnam
INO-4800[lower-alpha 7][113][114]
Inovio, CEPI, Korea National Institute of Health, International Vaccine Institute
South Korea, United States DNA vaccine (plasmid delivered by electroporation) Phase I–II (40)
Apr–Nov 2020, United States, South Korea
Preclinical
Pending Phase I report.
Unnamed[420]
Chinese Academy of Medical Sciences
China Inactivated SARS‑CoV‑2 vaccine Phase I–II (942)
Randomized, double-blinded, single-center, placebo-controlled
Jun 2020  Sep 2021, Chengdu
Preclinical
AG0301-COVID‑19[115]
AnGes Inc.,[421] AMED
Japan DNA vaccine (plasmid) Phase I–II (30)
Non-randomized, single-center, two doses
Jun 2020  Jul 2021, Osaka
Preclinical
Lunar-COV19/ARCT-021[422][423]
Arcturus Therapeutics, Duke–NUS Medical School
United States, Singapore RNA vaccine Phase I–II (92)
Randomized, double-blinded
Aug 2020  ?, Singapore
Preclinical
VLA2001[105][106]
Valneva
France Inactivated SARS‑CoV‑2 vaccine Phase I–II (150)
Randomized, multi-center, double-blinded
Dec 2020  Feb 2021, United Kingdom
Preclinical
COVID‑19/aAPC[118]
Shenzhen Genoimmune Medical Institute[424]
China Lentiviral vector vaccine (with minigene modifying aAPCs) Phase I (100)
Mar 2020  2023, Shenzhen
Preclinical
LV-SMENP-DC[119]
Shenzhen Genoimmune Medical Institute[424]
China Lentiviral vector vaccine (with minigene modifying DCs) Phase I (100)
Mar 2020  2023, Shenzhen
Preclinical
LNP-nCoVsaRNA[425]
MRC clinical trials unit at Imperial College London
United Kingdom RNA vaccine Phase I (105)
Randomized trial, with dose escalation study (15) and expanded safety study (at least 200)
Jun 2020  Jul 2021, United Kingdom
Preclinical
GRAd-COV2[426][427]
ReiThera, Lazzaro Spallanzani National Institute for Infectious Diseases
Italy Adenovirus vector vaccine (modified chimpanzee adenovirus vector, GRAd) Phase I (90)[428]
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
Preclinical
GX-19[116][117]
Genexine consortium,[429] International Vaccine Institute
South Korea DNA vaccine Phase I (40)
Jun 2020  Jun 2022, Seoul
Preclinical
SCB-2019[430][431]
Clover Biopharmaceuticals,[432] GSK, CEPI
China, United Kingdom Subunit vaccine (Spike protein trimeric subunit with AS03) Phase I (150)
Jun 2020  Mar 2021, Perth
Preclinical
COVAX-19[433]
Vaxine Pty Ltd[434]
Australia Subunit vaccine (recombinant protein) Phase I (40)
Jun 2020  Jul 2021, Adelaide
Preclinical
Unnamed[435]
PLA Academy of Military Science, Walvax Biotech[436]
China RNA vaccine Phase I (168)
Jun 2020  Dec 2021, China
Preclinical
HGC019[437]
Gennova Biopharmaceuticals, HDT Biotech Corporation[438]
India, United States RNA vaccine Phase I (120)[439]
Jan 2021  ?, India
Preclinical
Bangavax [440][441] Globe Biotech Ltd of Bangladesh Bangladesh RNA vaccine Phase I (100)[440][442]
Randomized, Parallel Group Trial
Feb 2021  Feb 2022,[443] Bangladesh
Preclinical
Unnamed[444]
Biological E. Limited, Baylor College of Medicine[445]
India, United States Inactivated SARS‑CoV‑2 vaccine (using an antigen) Phase I–II (360)[446]
Randomized, Parallel Group Trial
Nov 2020  Feb 2021, India
Preclinical
PTX-COVID19-B[447]
Providence Therapeutics
Canada RNA vaccine Phase I (60)[447]
Jan 2021  May 2021, Canada
Preclinical
COVAC-2[448]
VIDO (University of Saskatchewan)
Canada Subunit vaccine Phase I (108)[448]
Feb 2021  Jan 2022, Halifax
Preclinical
SARS-CoV-2 Sclamp/V451[110][111]
UQ, Syneos Health, CEPI, Seqirus
Australia Subunit vaccine (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[449] and V591/MV-SARS-CoV-2[450] Merck & Co. (Themis BIOscience), Institut Pasteur, University of Pittsburgh's Center for Vaccine Research (CVR), CEPI United States, France 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.[451]
  1. Latest phase with published results.
  2. US authorization also includes the three sovereign nations in the Compact of Free Association: Palau, the Marshall Islands, and Micronesia.[246][247]
  3. Serum Institute of India will be producing the ChAdOx1 nCoV-19 vaccine for India[293] and other low and middle income countries.[294]
  4. Oxford name: ChAdOx1 nCoV-19. Manufacturing in Brazil to be carried out by Oswaldo Cruz Foundation.[295]
  5. Latest Phase with published results.
  6. Virus-like particles grown in Nicotiana benthamiana[411]
  7. South Korean Phase I–II in parallel with Phase I in the US

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)[452]

The effectiveness of a new vaccine is defined by its efficacy during clinical trials.[207] The efficacy is the risk of getting the disease by vaccinated participants in the trial compared with the the risk of getting the disease by unvaccinated participants.[207] 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.[453] 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.[454] 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.[455][456]

Authorized and approved vaccines have shown the following efficacies:

At the University of Oxford, researchers have as of early February 2021 begun enrolling volunteers in an 820 person trial to evaluate the efficacy of combining two different vaccines, a mix and match approach, as opposed to using two doses of the same vaccine. The ultimate goal of the study will be find whether the mix and match method is just as or more effective than the currently used practice. The study will utilize the shot developed by Pfizer and BioNTech with the University of Oxford and AstraZeneca shot, two vaccines which rely on different methods to deliver information to the cells of the recipient. Ugur Sahin has voiced his opposition to the trial in December, stating that a study "will use up doses that people who need them could profit from, I am not happy about this," though Pfizer and AstraZeneca have supported the trials.[468]

Variants

In December 2020, a new SARS‑CoV‑2 variant, B.1.1.7, was identified in the UK.[469] Early results suggest that both the Pfizer and Moderna vaccines protect against the UK variant.[470][471] However they are less effective against the South Africa variant, with Moderna reporting that the current vaccine produced only one-sixth of the antibodies in response to the South African variant compared with the original virus. They have launched a trial of a new vaccine to tackle the South African 501.V2 variant (also known as B.1.351).[472] On 17 February 2021, Pfizer announced neutralization activity was reduced by two thirds for the 501.V2 variant, while stating no claims about the efficacy of the vaccine in preventing illness for this variant could yet be made.[473]

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.[474]

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.[475] 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.[476] 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.[477][478]

A preliminary study by Pfizer, Inc. has indicated that there is, at most, only minor reduction of the company's mRNA vaccine effectiveness against different SARS-CoV-2 variants.[479] Another study of the effectiveness of the same Comirnaty vaccine against the B.1.1.7 variant confirmed this.[480] According to the US CDC, most experts believe that, due to the nature of the virus, the emergence of variants that completely escape the immune response (both natural and vaccine induced) is considered unlikely.[97]

T-cell immunity is under investigation as a potential solution to the problem of reduced effectiveness of vaccines against the relevant variants. This is because T-cells target multiple pieces of the virus.[481] As the majority of genetic variation is on the spike protein, T-cells that attack other parts of the virus should be able to recognise new variants. Viral vector and mRNA based vaccines are believed to elicit the strongest t-cell response.[482] This believed to be the reason why the vaccine developed for yellow fever, an RNA virus like SARS-CoV-2, has remained effective for so long; by targeting antigens within the virus that are unlikely to change, as opposed to those on the surface, it is unaffected by the majority of mutations. Companies including Emergex, Osivax and eTheRNA are targeting these internal antigens in the hope of creating a "universal" SARS-CoV-2 vaccine.[483] Biotechnology firm Gritstone is also experimenting to develop a vaccine aimed specifically at creating T-cell immunity.[484][485]

On 29 January 2021, a deputy of the Moscow City Duma, Darya Besedina, turned to the Russian Minister of Health with a request to fund the study of new strains and conduct research on the effectiveness of Russian vaccines against these strains.[486] On 10 February 2021, the European Medicines Agency made a similar appeal to vaccine manufacturers.[487] On 15 February, Russian President Vladimir Putin instructed the government to deploy the sequencing of the genomes of Russian SARS-CoV-2 strains within a month, allocate funds for these studies, and also check whether Russian vaccines are effective against new strains.[488]

Formulation


As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity.[78] 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.[489] 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.[489][490] 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.[490] 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.[490] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines.[489][490]

Deployment


Location Vaccinated[lower-alpha 2] % of pop.[lower-alpha 3]
   World[lower-alpha 4]145,843,1491.9%
 United States49,772,18014.9%
 China[lower-alpha 5]40,520,000--
 EU21,168,2524.8%
 United Kingdom20,089,55129.6%
 India11,845,0750.9%
 Turkey6,869,9238.2%
 Brazil6,518,6283.1%
 United Arab Emirates[lower-alpha 5]6,020,461--
 Israel4,723,96654.6%
 Germany4,079,1074.9%
 Morocco3,435,9979.3%
 Chile3,305,21417.3%
 Bangladesh3,110,5251.9%
 France2,967,9374.4%
 Italy2,902,4554.8%
 Spain2,361,8525.1%
 Russia2,200,0001.5%
 Poland2,149,6075.7%
 Mexico1,889,6721.5%
 Canada[lower-alpha 5]1,778,405--
 Indonesia1,691,7240.6%
 Netherlands[lower-alpha 5]952,919--
 Serbia924,68313.6%
 Romania915,7614.8%
 Saudi Arabia[lower-alpha 5]780,667--
 Argentina731,5711.6%
 Hungary685,2477.1%
 Austria[lower-alpha 5]645,986--
 Portugal596,8125.9%
 Greece572,1745.5%
 Switzerland527,9796.1%
 Belgium493,5484.3%
 Sweden474,0284.7%
 Sri Lanka[lower-alpha 5]466,350--
 Denmark418,8707.2%
 Czech Republic413,4073.9%
 Nepal[lower-alpha 5]402,264--
 Finland370,8746.7%
 Norway318,7225.9%
 Slovakia305,8325.6%
 Bahrain298,17117.5%
 Ireland271,5945.5%
 Peru265,6080.8%
 Singapore250,0004.3%
 Bulgaria175,0662.5%
 Lithuania164,0896.0%
 Jordan[lower-alpha 5]150,000--
 Qatar[lower-alpha 5]140,000--
 Kuwait137,0003.2%
 Croatia135,7563.3%
 Colombia130,5780.3%
 Slovenia121,2895.8%
 Panama[lower-alpha 5]114,529--
 Maldives[lower-alpha 5]111,415--
 Myanmar103,1420.2%
 Estonia77,5365.8%
 Algeria[lower-alpha 5]75,000--
 Pakistan72,8820.0%
 South Africa70,5270.1%
 Azerbaijan65,0000.6%
 Costa Rica57,1621.1%
 Cyprus53,6176.1%
 Seychelles51,57752.5%
 Malta51,18611.6%
 Oman48,6411.0%
 Latvia45,0492.4%
 Barbados33,63311.7%
 Australia31,8940.1%
 Japan28,5300.0%
 Dominican Republic26,4000.2%
 Lebanon[lower-alpha 5]26,400--
 Luxembourg26,0894.2%
 Jersey26,02525.8%
 Senegal25,6530.2%
 Gibraltar23,51869.8%
 South Korea21,1770.0%
 Cayman Islands[lower-alpha 5]21,106--
 Belarus20,9440.2%
 Ecuador20,7840.1%
 Kazakhstan20,1570.1%
 Guernsey[lower-alpha 5]20,047--
 Hong Kong20,0000.3%
 Iceland19,5935.7%
 Zimbabwe18,8430.1%
 Isle of Man14,12316.6%
 Cambodia13,1010.1%
 Bermuda12,30419.8%
 Northern Cyprus[lower-alpha 5]11,000--
 Bolivia[lower-alpha 5]10,167--
 Albania[lower-alpha 5]10,135--
 Iran10,0000.0%
 Turks and Caicos Islands6,43316.6%
 El Salvador[lower-alpha 5]6,000--
 Faroe Islands4,1908.6%
 Mauritius3,8430.3%
 Malaysia[lower-alpha 5]3,580--
 Ukraine3,1410.0%
 Anguilla2,76218.4%
 Greenland2,5844.6%
 Guatemala[lower-alpha 5]2,490--
 Monaco[lower-alpha 5]2,400--
 Andorra2,3903.1%
 Liechtenstein[lower-alpha 5]2,218--
 Macau[lower-alpha 5]2,000--
 Guyana1,8520.2%
 Falkland Islands1,73249.7%
 New Zealand1,5000.0%
 Egypt[lower-alpha 5]1,315--
 Montenegro1,2880.2%
 Paraguay1,0000.0%
 Trinidad and Tobago4400.0%
 Venezuela1570.0%
 Saint Helena[lower-alpha 5]107--
 San Marino350.1%
 F.S. Micronesia[492]10,61910.2%
 Marshall Islands[492]8,81915.1%
 Palau[492]5,14328.7%

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. This country's data reflects total doses administered, not the first shot only.

As of 28 February 2021, 244.27 million COVID‑19 vaccine doses had been administered worldwide based on official reports from national health agencies collated by Our World in Data.[493]

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).[494] Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country.[495][496][497][498] Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need.[495][496][498] In April, 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.[499] 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.[498]

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."[500] 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.[494][501][502][503] 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.[504][505] 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.[500][502][504]

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".[506] The declaration is effective in the United States through 1 October 2024.[506]

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.[507] 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.[508]

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.[509]

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."[510]

The Chinese Sinopharm's COVID-19 vaccine was authorized for emergency use by Bahrain and the United Arab Emirates in December 2020.[511][512]

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.[513][514][515]

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[516]  which increases the risk of further viral spread that could lead to COVID‑19 outbreaks.[35] In mid-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, race, and geography.[517]

A poll conducted by National Geographic and Morning Consult demonstrated a gender gap on willingness to take a COVID‑19 vaccine in the U.S., with 69% of men polled saying they would take the vaccine, compared to only 51% of women. The poll also showed a positive correlation between education level and willingness to take the vaccine.[518]

In an effort to demonstrate the vaccine's safety, prominent politicians have received it on camera, with others pledging to do so.[519][520][521]

See also


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Further reading


Vaccine protocols