COVID-19 vaccine

From Wikipedia the free encyclopedia

Map showing share of population fully vaccinated against COVID-19 relative to a country's total population[needs update]
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 that causes coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020.[1] The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness.[2] 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.[3] The COVID‑19 vaccines are widely credited for their role in reducing the spread, severity, and death caused by COVID-19.[4]

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.[5] Single dose interim use is under consideration to extend vaccination to as many people as possible until vaccine availability improves.[6][7][8][9]

As of 15 September 2021, 5.82 billion doses of COVID‑19 vaccine have been administered worldwide based on official reports from national public health agencies.[10] AstraZeneca anticipates producing 3 billion doses in 2021, Pfizer–BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Janssen 1 billion doses each. Moderna targets producing 600 million doses and Convidecia 500 million doses in 2021.[11][12] By December 2020, more than 10 billion vaccine doses had been preordered by countries,[13] with about half of the doses purchased by high-income countries comprising 14% of the world's population.[14]

Background

A US airman receiving a COVID-19 vaccine, December 2020

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.[15] 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.[16] 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[17] and MERS[18] 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.[19][20][21] There is no cure or protective vaccine proven to be safe and effective against SARS in humans.[22][23] There is also no proven vaccine against MERS.[24] When MERS became prevalent, it was believed that existing SARS research might provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection.[22][25] As of March 2020, there was one (DNA-based) MERS vaccine which completed Phase I clinical trials in humans,[26] and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).[27]

As multiple COVID-19 vaccines have been authorized or licensed for use, real-world vaccine effectiveness (RWE) is now being assessed using case control and observational studies.[28] A study is investigating the long-lasting protection against SARS-CoV-2 provided by the mRNA vaccines.[29] On 10 August, a study showed that the full vaccination coverage rate is correlated inversely to the SARS-CoV-2 delta variant mutation frequency in 16 countries (R-squared=0.878).[30]

Formulation

As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity.[31] 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.[32] 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.[32][33] 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.[33] 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.[33] The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines.[32][33]

Clinical research

COVID-19 vaccine clinical research is the clinical research on COVID-19 vaccines, including their efficacy, effectiveness and safety. There are 22 vaccines authorized for use by national governments, with six vaccines being approved for emergency or full use by at least one WHO-recognised stringent regulatory authority; and five of them are in Phase IV. 204 vaccines under clinical trials that have not yet been authorized. There are also nine clinical trials on heterologous vaccination courses.

In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. Twenty vaccines are authorized by at least one national regulatory authority for public use: one DNA vaccine (ZyCoV-D) two RNA vaccines (Pfizer–BioNTech and Moderna), ten conventional inactivated vaccines (BBIBP-CorV, Chinese Academy of Medical Sciences, CoronaVac, Covaxin, CoviVac, COVIran Barekat, FAKHRAVAC, Minhai-Kangtai, QazVac, and WIBP-CorV), five viral vector vaccines (Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Janssen), and five protein subunit vaccines (Abdala, EpiVacCorona, MVC-COV1901, Soberana 02, and ZF2001).[34][35] In total, 330 vaccine candidates are in various stages of development, with 102 in clinical research, including 30 in Phase I trials, 30 in Phase I–II trials, 25 in Phase III trials, and 8 in Phase IV development.[34]

Post-vaccination complications

Post-vaccination embolic and thrombotic events, also termed vaccine-induced prothrombotic immune thrombocytopenia (VIPIT),[36] vaccine-induced immune thrombotic thrombocytopenia (VITT),[37][38] or thrombosis with thrombocytopenia syndrome (TTS)[39] are rare types of blood clotting syndromes that were initially observed in a very small number of people who had previously received the Oxford–AstraZeneca COVID-19 vaccine (AZD1222)[a] during the COVID-19 pandemic.[36][43] It was subsequently also described in the Janssen COVID-19 vaccine (Johnson & Johnson) leading to suspension of its use until its safety had been reassessed.[44]

In April 2021, AstraZeneca and the EMA updated their information for healthcare professionals about AZD1222, saying it was "considered plausible" that there was a causal relationship between the vaccination and the occurrence of thrombosis in combination with thrombocytopenia and that, "although such adverse reactions are very rare, they exceeded what would be expected in the general population".[43][45][46][47]

Guidelines from professional societies recommend treatment with alternative anticoagulants instead of heparin, as there is a possibility that it may aggravate the phenomenon.[48][49]

Vaccine types

Conceptual diagram showing three vaccine types for forming SARS‑CoV‑2 proteins to prompt an immune response: (1) RNA vaccine, (2) subunit vaccine, (3) viral vector vaccine
Vaccine platforms being employed for SARS-CoV-2. Whole virus vaccines include both attenuated and inactivated forms of the virus. Protein and peptide subunit vaccines are usually combined with an adjuvant in order to enhance immunogenicity. The main emphasis in SARS-CoV-2 vaccine development has been on using the whole spike protein in its trimeric form, or components of it, such as the RBD region. Multiple non-replicating viral vector vaccines have been developed, particularly focused on adenovirus, while there has been less emphasis on the replicating viral vector constructs.[50]

At least nine different technology platforms are under research and development to create an effective vaccine against COVID‑19.[51][31] 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,[31], since the S protein triggers immune responses.[52] 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.[15][31][53][54]

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 precise targeting of COVID‑19 infection mechanisms.[31][53][54] Several of the synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an adaptive immune response to the virus before it attaches to a human cell.[55] 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 weakened immune systems.[31][53]

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.

Several COVID-19 vaccines, including the Pfizer–BioNTech and Moderna vaccines, have been developed to use RNA to stimulate an immune response. When introduced into human tissue, the RNA contained in the vaccine acts as messenger RNA (mRNA) to cause cells to build the SARS-CoV-2 spike protein. This teaches the body how to identify and destroy the corresponding pathogen. 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.[56][57][58][59]

RNA vaccines were the first COVID‑19 vaccines to be authorized in the United Kingdom, the United States and the European Union.[60][61] Authorized vaccines of this type are the Pfizer–BioNTech[62][63][64] and Moderna vaccines.[65][66] The CVnCoV RNA vaccine from CureVac failed in clinical trails.[67]

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.[68] For 4,041,396 Moderna COVID‑19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported.[68] The lipid nanoparticles were most likely responsible for the allergic reactions.[68]

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.[69][70] 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.[69]

Authorized vaccines of this type are the Oxford–AstraZeneca COVID-19 vaccine,[71][72][73] the Sputnik V COVID-19 vaccine,[74] Convidecia, and the Janssen COVID-19 vaccine.[75][76]

Convidecia and the Janssen COVID-19 vaccine are both one-shot vaccines which offer less complicated logistics and can be stored under ordinary refrigeration for several months.[77][78]

Sputnik V uses Ad26 for its first dose, which is the same as Janssen's only dose, and Ad5 for the second dose, which is the same as Convidecia's only dose.[79]

On 11 August 2021, the developers of Sputnik V proposed, in view of the Delta case surge that Pfizer test the Ad26 component (termed its ‘Light’ version)[80] as a booster shot:

Delta cases surge in US & Israel shows mRNA vaccines need a heterogeneous booster to strengthen & prolong immune response. #SputnikV pioneered mix&match approach, combo trials & showed 83.1% efficacy vs Delta. Today RDIF offers Pfizer to start trial with Sputnik Light as booster.[81]

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.[82]

Authorized vaccines of this type are the Chinese CoronaVac,[83][84][85] BBIBP-CorV,[86] and WIBP-CorV; the Indian Covaxin; later this year the Russian CoviVac;[87] the Kazakhstani vaccine QazVac;[88] and the Iranian COVIran Barekat.[89] Vaccines in clinical trials include the Valneva COVID-19 vaccine.[90][unreliable source?][91]

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.[92]

The three authorized vaccines of this type are the peptide vaccine EpiVacCorona,[93] ZF2001,[51] and MVC-COV1901.[94] Vaccines with pending authorizations include the Novavax COVID-19 vaccine,[95] 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.[96][97]

Intranasal

Intranasal vaccines target mucosal immunity in the nasal mucosa which is a portal for viral entrance to the body.[98][99] These vaccines are designed to stimulate nasal immune factors, such as IgA.[98] In addition to inhibiting the virus, nasal vaccines provide ease of administration because no needles (and the accompanying needle phobia) are involved.[99][100] Nasal vaccines have been approved for other infections, such as influenza.[99][100] As of 2021, only one nasal vaccine, Flumist (USA); Fluenz Tetra (European Union), had been authorized in the United States and Europe for use as an influenza vaccine.[100][101]

Other types

Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines,[102][103][104][105][106][107] at least two lentivirus vector vaccines,[108][109] a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.[110]

Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID‑19 infection.[111] 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.[112]

Planning and development

Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[31]

Multiple steps along the entire development path are evaluated, including:[15][113]

  • 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.[114] Public health programs have been described as in "[a] race to vaccinate individuals" with the early wave vaccines.[115]

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.[114][116] As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020,[117] 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.[114][118]

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.[53][54][119] Additionally, research at universities is obstructed by physical distancing and closing of laboratories.[120][121]

Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels and adverse effects of the candidate vaccine.[122][123] 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 rates across and within countries, forcing companies to compete for trial participants.[124] Clinical trial organizers also may encounter people unwilling to be vaccinated due to vaccine hesitancy[125] or disbelief in the science of the vaccine technology and its ability to prevent infection.[126] 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.[127][128][129]

Organizations

Internationally, the Access to COVID-19 Tools Accelerator is a G20 and World Health Organization (WHO) initiative announced in April 2020.[130][131] 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.[132] 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.[133]

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,[134] and to support clinical trials and develop manufacturing and supply chains for vaccines.[135]

China provided low-rate loans to one vaccine developer through its central bank, and "quickly made land available for the company" to build production plants.[116] Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing.[136]

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.[137]

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.[116][138] In May 2020, the government announced funding for a fast-track program called Operation Warp Speed.[139][140] By March 2021, BARDA had funded an estimated $19.3 billion in COVID-19 vaccine development.[141]

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 towards effective vaccines.[116][114]

History

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

COVID-19's caused virus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), was isolated in late 2019.[142] 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.[143][144][145] Since 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[146] 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.[144][147][148][149] According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development shows North American entities to have about 40% of the activity, compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.[143][146]

In February 2020, the World Health Organization (WHO) said it did not expect a vaccine against SARS‑CoV‑2 to become available in less than 18 months.[150] Virologist Paul Offit commented that, in hindsight, the development of a safe and effective vaccine within 11 months was a remarkable feat.[151] The rapidly growing infection rate of COVID‑19 worldwide during 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines,[152] with four vaccine candidates entering human evaluation in March (see COVID-19 vaccine § Trial and authorization status).[143][153]

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.[154] 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.[155]

The Pfizer–BioNTech partnership submitted an Emergency Use Authorization (EUA) request to the U.S. Food and Drug Administration (FDA) for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020.[156][157] On 2 December 2020, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine,[158][159] becoming the first country to approve the vaccine and the first country in the Western world to approve the use of any COVID‑19 vaccine.[160][161][162] As of 21 December 2020, many countries and the European Union[163] had 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.[164][165] On 11 December 2020, the FDA granted an EUA for the Pfizer–BioNTech COVID‑19 vaccine.[166] A week later, they granted an EUA for mRNA-1273 (active ingredient elasomeran), the Moderna vaccine.[167][168][169][170]

On 31 March 2021, the Russian government announced that they had registered the first COVID‑19 vaccine for animals.[171] Named Carnivac-Cov, it is an inactivated vaccine for carnivorous animals, including pets, aimed at preventing mutations that occur during the interspecies transmission of SARS-CoV-2.[172]

In June 2021, a report revealed that the UB-612 vaccine, developed by the US-based COVAXX, was a venture initiated for profits by the Blackwater founder Erik Prince. In a series of text messages to Paul Behrends, the close associate recruited for the COVAXX project, Prince described the profit-making possibilities in selling the COVID‑19 vaccines. COVAXX provided no data from the clinical trials on safety or efficacy. The responsibility of creating distribution networks was assigned to an Abu Dhabi-based entity, which was mentioned as "Windward Capital" on the COVAXX letterhead but was actually Windward Holdings. The sole shareholder of the firm, which handled "professional, scientific and technical activities", was Erik Prince. In March 2021, COVAXX raised $1.35 billion in a private placement.[173]

Side effects

Serious adverse events associated with receipt of new vaccines targeting COVID-19 are of high interest to the public.[174] All vaccines that are administered via intramuscular injection, including COVID-19 vaccines, have side effects related to the mild trauma associated with the procedure and introduction of a foreign substance into the body.[175] These include soreness, redness, rash, and inflammation at the injection site. Other common side effects include fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain) which generally resolve within a few days.[176] One less-frequent side effect (that generally occurs in less than 1 in 1,000 people) is hypersensitivity (allergy) to one or more of the vaccine's ingredients, which in some rare cases may cause anaphylaxis.[177][178][179][180]

Society and culture

Distribution

Location Vaccinated[b] %[c]
World[d] 3,351,340,728 42.6%
China China 1,095,000,000 75.8%
India India 576,856,263 41.4%
European Union European Union 295,017,924 66.0%
United States United States[e] 210,361,099 62.5%
Brazil Brazil 143,732,460 67.2%
Japan Japan 82,148,564 65.2%
Indonesia Indonesia 75,140,724 27.2%
Mexico Mexico 61,407,799 47.1%
Germany Germany 55,595,233 66.3%
Pakistan Pakistan 52,798,836 23.4%
Turkey Turkey 52,153,868 61.3%
France France 49,630,717 73.5%
United Kingdom United Kingdom 48,480,178 71.1%
Russia Russia 46,427,518 31.8%
Italy Italy[f] 43,994,525 72.9%
Spain Spain 37,303,202 79.8%
South Korea South Korea 34,977,073 68.2%
Argentina Argentina 28,819,589 63.2%
Canada Canada 28,486,874 74.8%
Thailand Thailand 27,769,095 39.7%
Vietnam Vietnam 25,420,169 25.9%
Colombia Colombia 24,613,353 48.0%
Iran Iran 22,943,141 27.0%
Saudi Arabia Saudi Arabia 22,932,990 64.9%
Malaysia Malaysia 21,721,344 66.3%
Bangladesh Bangladesh 21,323,646 12.8%
Morocco Morocco 19,884,992 53.2%
Poland Poland 19,561,992 51.8%
Philippines Philippines 18,697,647 16.8%
Chile Chile 14,574,727 75.9%
Australia Australia 14,367,430 55.7%
Sri Lanka Sri Lanka 13,602,365 63.3%
Peru Peru 12,213,452 36.6%
Netherlands Netherlands 12,048,955 70.2%
Cambodia Cambodia 11,506,197 67.9%
Taiwan Taiwan 11,483,332 48.1%
South Africa South Africa 11,206,776 18.7%
Ecuador Ecuador 10,699,102 59.8%
Uzbekistan Uzbekistan 9,787,973 28.8%
United Arab Emirates United Arab Emirates 9,010,208 90.2%
Portugal Portugal 8,840,653 87.0%
Belgium Belgium 8,504,951 73.1%
Egypt Egypt 7,743,420 7.4%
Kazakhstan Kazakhstan 7,160,129 37.7%
Cuba Cuba 7,141,985 63.1%
Sweden Sweden 7,037,966 69.3%
Venezuela Venezuela 6,822,809 23.8%
Greece Greece 6,319,108 60.9%
Ukraine Ukraine 6,097,683 14.0%
Israel Israel 6,055,327 68.9%
Czech Republic Czechia 6,023,270 56.2%
Nepal Nepal 6,004,019 20.2%
Dominican Republic Dominican Republic 5,934,452 54.2%
Hungary Hungary 5,850,887 60.7%
Algeria Algeria 5,815,039 13.0%
Austria Austria 5,630,639 62.3%
Romania Romania 5,331,254 27.9%
Switzerland Switzerland 5,220,976 59.9%
Singapore Singapore 4,648,305 78.8%
Tunisia Tunisia 4,574,648 38.3%
Azerbaijan Azerbaijan 4,551,501 44.5%
Myanmar Myanmar 4,456,857 8.1%
Denmark Denmark 4,437,113 76.3%
Hong Kong Hong Kong 4,367,360 57.8%
Bolivia Bolivia 4,149,398 35.1%
Finland Finland 4,085,588 73.6%
Nigeria Nigeria 4,024,704 1.9%
Norway Norway 3,994,375 73.1%
Guatemala Guatemala 3,931,445 21.5%
El Salvador El Salvador 3,861,053 59.2%
Republic of Ireland Ireland 3,740,175 75.1%
Iraq Iraq 3,684,546 8.9%
Jordan Jordan 3,605,788 35.1%
Costa Rica Costa Rica 3,144,786 61.2%
Serbia Serbia 2,981,529 43.8%
New Zealand New Zealand 2,978,105 61.3%
Honduras Honduras 2,947,650 29.3%
Zimbabwe Zimbabwe 2,891,837 19.2%
Panama Panama 2,875,314 65.6%
Uruguay Uruguay 2,712,408 77.8%
Kuwait Kuwait 2,668,082 61.6%
Laos Laos 2,650,948 35.9%
Oman Oman 2,592,464 49.6%
Paraguay Paraguay 2,439,006 33.8%
Slovakia Slovakia 2,407,907 44.1%
Ethiopia Ethiopia 2,366,290 2.0%
Qatar Qatar 2,360,308 80.5%
Kenya Kenya 2,353,534 4.3%
Mongolia Mongolia 2,247,754 67.5%
Tajikistan Tajikistan 2,168,537 22.2%
Mozambique Mozambique 1,864,229 5.8%
Rwanda Rwanda 1,827,371 13.8%
Croatia Croatia 1,766,447 43.3%
Lithuania Lithuania 1,712,315 63.7%
Belarus Belarus 1,692,439 17.9%
Angola Angola 1,510,880 4.5%
Lebanon Lebanon 1,479,033 21.9%
Libya Libya 1,246,217 17.9%
Senegal Senegal 1,203,066 7.0%
Ivory Coast Ivory Coast 1,193,877 4.4%
State of Palestine Palestine 1,185,157 22.7%
Bahrain Bahrain 1,159,039 66.3%
Bulgaria Bulgaria 1,089,066 15.8%
Slovenia Slovenia 1,055,228 50.8%
Uganda Uganda 1,030,447 2.2%
Guinea Guinea 945,741 7.0%
Georgia (country) Georgia 914,222 23.0%
Albania Albania 904,594 31.5%
Latvia Latvia 885,058 47.4%
Ghana Ghana 865,422 2.8%
Mauritius Mauritius 842,642 66.2%
Afghanistan Afghanistan 773,002 1.9%
North Macedonia North Macedonia 763,966 36.7%
Kyrgyzstan Kyrgyzstan 753,735 11.4%
Estonia Estonia 742,961 56.1%
Malawi Malawi 725,381 3.7%
Kosovo Kosovo 704,318 36.4%
Sudan Sudan 646,192 1.4%
Bosnia and Herzegovina Bosnia and Herzegovina 634,063 19.4%
Cyprus Cyprus 588,112 66.2%
Moldova Moldova 573,001 14.2%
Fiji Fiji 569,958 63.1%
Bhutan Bhutan 567,175 72.7%
Trinidad and Tobago Trinidad and Tobago 551,160 39.3%
Jamaica Jamaica 498,580 16.8%
Nicaragua Nicaragua 476,308 7.1%
Malta Malta 417,684 81.2%
Luxembourg Luxembourg 416,918 65.7%
Togo Togo 414,249 4.9%
Niger Niger 404,246 1.6%
East Timor Timor-Leste 399,214 29.7%
Maldives Maldives 389,821 71.7%
Botswana Botswana 365,655 15.2%
Cameroon Cameroon 363,773 1.3%
Zambia Zambia 354,752 1.9%
Tanzania Tanzania 350,000 0.6%
Guyana Guyana 337,030 42.6%
Macau Macao 332,204 50.5%
Mauritania Mauritania 311,544 6.5%
Yemen Yemen 308,025 1.0%
Mali Mali 284,052 1.4%
Iceland Iceland 280,889 81.8%
Cape Verde Cabo Verde 272,501 48.5%
Brunei Brunei 237,015 53.7%
Namibia Namibia 232,051 9.0%
Montenegro Montenegro 224,708 35.8%
Somalia Somalia 223,498 1.4%
Armenia Armenia 215,278 7.2%
Suriname Suriname 214,886 36.3%
Madagascar Madagascar 210,666 0.7%
Equatorial Guinea Equatorial Guinea 210,358 14.5%
Republic of the Congo Congo 207,265 3.7%
Syria Syria 201,379 1.1%
Sierra Leone Sierra Leone 181,065 2.2%
Eswatini Eswatini 180,709 15.4%
The Gambia Gambia 179,910 7.2%
Belize Belize 177,480 43.8%
Comoros Comoros 174,765 19.7%
Burkina Faso Burkina Faso 166,160 0.8%
Northern Cyprus Northern Cyprus 160,361 42.0%
Benin Benin 152,669 1.2%
French Polynesia French Polynesia 146,890 52.0%
Barbados Barbados 122,509 42.6%
Papua New Guinea Papua New Guinea 114,419 1.2%
The Bahamas Bahamas 105,753 26.6%
Liberia Liberia 104,545 2.0%
Central African Republic Central African Republic 102,591 2.1%
Guernsey Guernsey 101,290[g]
New Caledonia New Caledonia 101,168 35.1%
Curaçao Curaçao 97,148 59.0%
Samoa Samoa 97,032 48.5%
Chad Chad 86,821 0.5%
Democratic Republic of the Congo Democratic Republic of the Congo 85,182 0.1%
Gabon Gabon 84,214 3.7%
Aruba Aruba 80,491 75.1%
Jersey Jersey 76,723 75.9%
Seychelles Seychelles 74,719 75.5%
Solomon Islands Solomon Islands 74,573 10.6%
Lesotho Lesotho 71,597 3.3%
Isle of Man Isle of Man 65,428 76.6%
South Sudan South Sudan 55,182 0.5%
Cayman Islands Cayman Islands 53,934 81.1%
Andorra Andorra 51,599 66.7%
São Tomé and Príncipe Sao Tome and Principe 45,088 20.2%
Antigua and Barbuda Antigua and Barbuda 43,681 44.2%
Bermuda Bermuda 43,377 69.9%
Saint Lucia Saint Lucia 42,145 22.9%
Tonga Tonga 41,130 38.5%
Greenland Greenland 40,730 71.6%
Djibouti Djibouti 39,923 4.0%
Gibraltar Gibraltar 39,808 118.2%
Vanuatu Vanuatu 39,347 12.5%
Faroe Islands Faroe Islands 37,447 76.3%
Haiti Haiti 36,583 0.3%
Turkmenistan Turkmenistan 32,240 0.5%
Grenada Grenada 28,511 25.2%
Guinea-Bissau Guinea-Bissau 28,097 1.4%
Turks and Caicos Islands Turks and Caicos Islands 27,220 69.4%
Monaco Monaco 26,451 66.9%
Sint Maarten Sint Maarten 25,516 58.8%
Saint Kitts and Nevis Saint Kitts and Nevis 24,800 46.3%
Kiribati Kiribati 24,429 20.1%
San Marino San Marino 24,329 71.5%
Liechtenstein Liechtenstein 23,645 61.8%
Dominica Dominica 22,930 31.8%
Saint Vincent and the Grenadines Saint Vincent and the Grenadines 19,512 17.5%
Caribbean Netherlands Caribbean Netherlands 19,109 72.3%
British Virgin Islands British Virgin Islands 18,405 60.5%
Cook Islands Cook Islands 11,416 65.0%
Anguilla Anguilla 9,493 62.8%
Nauru Nauru 7,612 70.0%
Tuvalu Tuvalu 6,167 51.7%
Wallis and Futuna Wallis and Futuna 4,952 44.6%
Saint Helena, Ascension and Tristan da Cunha St. Helena, Ascension, Tristan 4,361 71.8%
Falkland Islands Falkland Islands 2,632 75.6%
Montserrat Montserrat 1,466 29.4%
Niue Niue 1,184 73.2%
Tokelau Tokelau 968 70.8%
Pitcairn Islands Pitcairn 47 100.0%
  1. ^ The Oxford–AstraZeneca COVID-19 vaccine is codenamed AZD1222,[40] and later supplied under trade names, including Vaxzevria[41] and Covishield.[42]
  2. ^ Number of people 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. May include vaccination of non-citizens, which can push totals beyond 100% of the local population.
  4. ^ Countries which do not report the number of people who have received at least one dose are not included in the world total.
  5. ^ Includes Freely Associated States
  6. ^ Includes Vatican City
  7. ^ This country's data are the number of vaccine doses administered, not the first dose only.

As of 1 September 2021, 5.34 billion COVID-19 vaccine doses had been administered worldwide, with 39.6 per cent of the global population having received at least one dose. While 40.5 million vaccines were then being administered daily, only 1.8 per cent of people in low-income countries had received at least a first vaccine by September 2021, according to official reports from national health agencies, which is collated by Our World in Data.[182]

During a pandemic on the rapid timeline and scale of COVID-19 cases in 2020, international organizations like the World Health Organization (WHO) and Coalition for Epidemic Preparedness Innovations (CEPI), vaccine developers, governments, and industry evaluated the distribution of the eventual vaccine(s).[183] Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country.[184][185][186][187] Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need.[184][185][187]

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.[188] Several companies planned 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.[187]

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."[189] 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.[183][190][191][192] For example, successful COVID‑19 vaccines would be allocated early 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.[193][194]

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.[14]

Production of Sputnik V vaccine in Brazil, January 2021.
An elderly man receiving second dose of CoronaVac vaccine in Brazil, April 2021.

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."[195]

In March, it was revealed the US attempted to convince Brazil not to purchase the Sputnik V COVID-19 vaccine, fearing "Russian influence" in Latin America.[196] Some nations involved in long-standing territorial disputes have reportedly had their access to vaccines blocked by competing nations; Palestine has accused Israel of blocking vaccine delivery to Gaza, while Taiwan has suggested that China has hampered its efforts to procure vaccine doses.[197][198][199]

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 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.[200]

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."[201] Edward Bergmark and Arick Wierson are calling for a 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 the vaccines could be less effective.[202]

On 10 March 2021, the United States, Britain, European Union nations and other WTO members blocked a push by more than eighty developing countries to waive COVID‑19 vaccine patent rights in an effort to boost production of vaccines for poor nations.[203] On 5 May 2021, the Biden administration announced that it supports waiving intellectual property protections for COVID-19 vaccines.[204] The Members of the European Parliament have backed a motion demanding the temporary lifting of intellectual properties rights for COVID‑19 vaccines.[205] Commission vice-president Valdis Dombrovskis, stressed that while the EU is ready to discuss the issue of patent waivers, its proposed solutions include limiting export restrictions, resolving production bottlenecks, looking into compulsory licensing, investing in manufacturing capacity in developing countries and increasing contributions to the COVAX scheme.[206]

COVID-19 mass vaccination queue in Finland, June 2021.
A drive-thorugh COVID-19 vaccination center in Iran, August 2021.

In a meeting in April 2021, the World Health Organization's emergency committee addressed concerns of persistent inequity in the global vaccine distribution.[207] Although 9 percent of the world's population lives in the 29 poorest countries, these countries had received only 0.3% of all vaccines administered as of May 2021.[208] On 15 March, Brazilian journalism agency Agência Pública reported that the country vaccinated about twice as many people who declare themselves white than black and noted that mortality from COVID-19 is higher in the black population.[209]

In May 2021, UNICEF made an urgent appeal to industrialised nations to pool their excess COVID-19 vaccine capacity to make up for a 125-million-dose gap in the COVAX program. The program mostly relied on the Oxford–AstraZeneca COVID-19 vaccine produced by Serum Institute of India, which faced serious supply problems due to increased domestic vaccine needs in India from March to June 2021. Only a limited amount of vaccines can be distributed efficiently, and the shortfall of vaccines in South America and parts of Asia are due to a lack of expedient donations by richer nations. International aid organisations have pointed at Nepal, Sri Lanka, and Maldives as well as Argentina and Brazil, and some parts of the Caribbean as problem areas, where vaccines are in short supply. UNICEF has also been critical towards proposed donations of Moderna and Pfizer vaccines since these are not slated for delivery until the second half of 2021, or early 2022.[210]

On 1 July 2021, the heads of the World Bank Group, International Monetary Fund, World Health Organization and World Trade Organization said in a joint statement: "As many countries are struggling with new variants and a third wave of COVID-19 infections, accelerating access to vaccines becomes even more critical to ending the pandemic everywhere and achieving broad-based growth. We are deeply concerned about the limited vaccines, therapeutics, diagnostics, and support for deliveries available to developing countries."[211][212] In July 2021, The BMJ reported that countries have thrown out over 250,000 vaccine doses as supply exceeded demand and strict laws prevented the sharing of vaccines.[213] A survey by The New York Times found that over a million doses of vaccine had been thrown away in ten U.S. states because federal regulations prohibit recalling them, preventing their redistribution abroad.[214] Furthermore, doses donated close to expiration often cannot be administered quickly enough by recipient countries and end up having to be discarded.[215]

Amnesty International and Oxfam International have criticized the support of vaccine monopolies by the governments of producing countries, noting that this is dramatically increasing the dose price by 5 times and often much more, creating an economic barrier to access for poor countries.[216][217]

On 4 August 2021, to reduce unequal distribution between rich and poor countries, the WHO called for a moratorium on a booster dose at least until the end of September. However, on 18 August, the United States government announced plans to offer booster doses 8 months after the initial course to the general population, starting with priority groups. Before the announcement, the WHO harshly criticized this type of decision, citing the lack of evidence for the need for boosters, except for patients with specific conditions. At this time, vaccine coverage of at least one dose was 58% in high-income countries and only 1.3% in low-income countries, and 1.14 million Americans already received an unauthorized booster dose. US officials argued that waning efficacy against mild and moderate disease might indicate reduced protection against severe disease in the coming months. Israel, France, Germany and the United Kingdom have also started planning boosters for specific groups.[218][219][220]

Optimizing the societal benefit of vaccination may benefit from a strategy that is tailored to the state of the pandemic, the demographics of a country, the age of the recipients, the availability of vaccines, and the individual risk for severe disease: In the UK, the interval between prime and boost dose was extended to vaccinate as many persons as early as possible,[221] many countries are starting to give an additional booster shot to the immunosuppressed[222][223] and the elderly,[224] and research predicts an additional benefit of personalizing vaccine dose in the setting of limited vaccine availability when a wave of virus Variants of Concern hits a country.[225]

While vaccines substantially reduce the probability of infection, it is still possible for fully vaccinated people to contract and spread COVID-19.[226] Public health agencies have recommended that vaccinated people continue using preventive measures (wear face masks, social distance, wash hands) to avoid infecting others, especially vulnerable people, particularly in areas with high community spread. Governments have indicated that such recommendations will be reduced as vaccination rates increase and community spread declines.[227]

Inside of a vaccination center in Brussels, Belgium, February 2021.

Liability

There are liability shields in place to protect pharmaceutical companies like Pfizer and Moderna from negligence claims related to COVID-19 vaccines (and treatments). These liability shields took effect on 4 February 2020, when the US Secretary of Health and Human Services Alex Azar published a notice of declaration under the Public Readiness and Emergency Preparedness Act (PREP 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". 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". In other words, absent "willful misconduct", these companies can not be sued for money damages for any injuries that occur between 2020 and 2024 from the administration of vaccines and treatments related to COVID-19.[228] The declaration is effective in the United States through 1 October 2024.[228]

In December 2020, the UK government granted Pfizer legal indemnity for its COVID-19 vaccine.[229]

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.[230] 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.[231]

The Bureau of Investigative Journalism, a nonprofit news organization, reported in an investigation that unnamed officials in some countries, such as Argentina and Brazil, said that Pfizer demanded guarantees against costs of legal cases due to adverse effects in the form of liability waivers and sovereign assets such as federal bank reserves, embassy buildings or military bases, going beyond the expected from other countries such as the US.[232] During the pandemic parliamentary inquiry in Brazil, Pfizer's representative said that its terms for Brazil are the same as for all other countries with which it has signed deals.[233]

Misinformation and hesitancy

Anti-vaccination activists and other people in multiple countries have spread a variety of unfounded conspiracy theories based on misunderstood science, religion and other factors. Theories 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 have proliferated among masses making them averse to vaccination. This has led to governments around the world introducing measures to encourage vaccination.

Fake vaccines containing salt water have also been administered in some countries.[234][235][236]

See also

References

  1. ^ Li YD, Chi WY, Su JH, Ferrall L, Hung CF, Wu TC (December 2020). "Coronavirus vaccine development: from SARS and MERS to COVID-19". Journal of Biomedical Science. 27 (1): 104. doi:10.1186/s12929-020-00695-2. PMC 7749790. PMID 33341119.
  2. ^ Subbarao K (July 2021). "The success of SARS-CoV-2 vaccines and challenges ahead". Cell Host & Microbe. 29 (7): 1111–1123. doi:10.1016/j.chom.2021.06.016. PMC 8279572. PMID 34265245.
  3. ^ Padilla TB (24 February 2021). "No one is safe unless everyone is safe". BusinessWorld. Retrieved 24 February 2021.
  4. ^ Vergano D (5 June 2021). "COVID-19 Vaccines Work Way Better Than We Had Ever Expected. Scientists Are Still Figuring Out Why". BuzzFeed News. Retrieved 24 June 2021.
  5. ^ Beaumont P (18 November 2020). "Covid-19 vaccine: who are countries prioritising for first doses?". The Guardian. ISSN 0261-3077. Retrieved 26 December 2020.
  6. ^ Plotkin SA, Halsey N (January 2021). "Accelerate COVID-19 Vaccine Rollout by Delaying the Second Dose of mRNA Vaccines". Clinical Infectious Diseases. doi:10.1093/cid/ciab068. PMC 7929065. PMID 33502467.
  7. ^ Epperly D (January 2021). "Evidence For COVID-19 Vaccine Deferred Dose 2 Boost Timing". SSRN 3760833.
  8. ^ Wang X (April 2021). "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine". The New England Journal of Medicine (letter). 384 (16): 1577–1578. doi:10.1056/NEJMc2036242. PMID 33596350.
  9. ^ "More Evidence: Evidence For COVID-19 Vaccine Deferred Dose 2 Boost Timing". ReallyCorrect.com. 25 May 2021.
  10. ^ Ritchie, Hannah; Mathieu, Edouard; Rodés-Guirao, Lucas; Appel, Cameron; Giattino, Charlie; Ortiz-Ospina, Esteban; Hasell, Joe; MacDonald, Bobbie; Beltekian, Diana; Roser, Max (5 March 2020). "Coronavirus (COVID-19) Vaccinations – Statistics and Research". Our World in Data. Retrieved 7 February 2021.
  11. ^ Buntz B (5 February 2021). "Which companies will likely produce the most COVID-19 vaccine in 2021?". Pharmaceutical Processing World. Retrieved 1 March 2021.
  12. ^ "China can hit 500-mln-dose annual capacity of CanSinoBIO COVID-19 vaccine this year". Yahoo Sports. Reuters. 27 February 2021. Retrieved 1 March 2021.
  13. ^ Mullard A (November 2020). "How COVID vaccines are being divvied up around the world". Nature. doi:10.1038/d41586-020-03370-6. PMID 33257891. S2CID 227246811.
  14. ^ a b So AD, Woo J (December 2020). "Reserving coronavirus disease 2019 vaccines for global access: cross sectional analysis". BMJ. 371: m4750. doi:10.1136/bmj.m4750. PMC 7735431. PMID 33323376.
  15. ^ a b c Gates B (30 April 2020). "The vaccine race explained: What you need to know about the COVID-19 vaccine". The Gates Notes. Archived from the original on 14 May 2020. Retrieved 2 May 2020.
  16. ^ Cavanagh D (December 2003). "Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus". Avian Pathology. 32 (6): 567–82. doi:10.1080/03079450310001621198. PMC 7154303. PMID 14676007.
  17. ^ Gao W, Tamin A, Soloff A, D'Aiuto L, Nwanegbo E, Robbins PD, et al. (December 2003). "Effects of a SARS-associated coronavirus vaccine in monkeys". Lancet. 362 (9399): 1895–96. doi:10.1016/S0140-6736(03)14962-8. PMC 7112457. PMID 14667748.
  18. ^ Kim E, Okada K, Kenniston T, Raj VS, AlHajri MM, Farag EA, et al. (October 2014). "Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice". Vaccine. 32 (45): 5975–82. doi:10.1016/j.vaccine.2014.08.058. PMC 7115510. PMID 25192975.
  19. ^ Greenough TC, Babcock GJ, Roberts A, Hernandez HJ, Thomas WD, Coccia JA, et al. (February 2005). "Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice". The Journal of Infectious Diseases. 191 (4): 507–14. doi:10.1086/427242. PMC 7110081. PMID 15655773.
  20. ^ Tripp RA, Haynes LM, Moore D, Anderson B, Tamin A, Harcourt BH, et al. (September 2005). "Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): identification of neutralizing and antibodies reactive to S, N, M and E viral proteins". Journal of Virological Methods. 128 (1–2): 21–28. doi:10.1016/j.jviromet.2005.03.021. PMC 7112802. PMID 15885812.
  21. ^ Roberts A, Thomas WD, Guarner J, Lamirande EW, Babcock GJ, Greenough TC, et al. (March 2006). "Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters". The Journal of Infectious Diseases. 193 (5): 685–92. doi:10.1086/500143. PMC 7109703. PMID 16453264.
  22. ^ a b Jiang S, Lu L, Du L (January 2013). "Development of SARS vaccines and therapeutics is still needed". Future Virology. 8 (1): 1–2. doi:10.2217/fvl.12.126. PMC 7079997. PMID 32201503.
  23. ^ "SARS (severe acute respiratory syndrome)". National Health Service. 5 March 2020. Archived from the original on 9 March 2020. Retrieved 31 January 2020.
  24. ^ Shehata MM, Gomaa MR, Ali MA, Kayali G (June 2016). "Middle East respiratory syndrome coronavirus: a comprehensive review". Frontiers of Medicine. 10 (2): 120–36. doi:10.1007/s11684-016-0430-6. PMC 7089261. PMID 26791756.
  25. ^ Butler D (October 2012). "SARS veterans tackle coronavirus". Nature. 490 (7418): 20. Bibcode:2012Natur.490...20B. doi:10.1038/490020a. PMID 23038444.
  26. ^ Modjarrad K, Roberts CC, Mills KT, Castellano AR, Paolino K, Muthumani K, et al. (September 2019). "Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial". The Lancet. Infectious Diseases. 19 (9): 1013–22. doi:10.1016/S1473-3099(19)30266-X. PMC 7185789. PMID 31351922.
  27. ^ Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS (2019). "Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus". Frontiers in Microbiology. 10: 1781. doi:10.3389/fmicb.2019.01781. PMC 6688523. PMID 31428074.
  28. ^ Bok K, Sitar S, Graham BS, Mascola JR (August 2021). "Accelerated COVID-19 vaccine development: milestones, lessons, and prospects". Immunity. 54 (8): 1636–1651. doi:10.1016/j.immuni.2021.07.017. PMC 8328682. PMID 34348117.
  29. ^ Turner JS, O'Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, et al. (August 2021). "SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses". Nature. 596 (7870): 109–113. Bibcode:2021Natur.596..109T. doi:10.1038/s41586-021-03738-2. PMID 34182569. Lay summary.
  30. ^ Yeh TY, Contreras, GP (10 August 2021). "Full vaccination suppresses SARS-CoV-2 delta variant mutation frequency". medRxiv. doi:10.1101/2021.08.08.21261768. S2CID 236965312.
  31. ^ a b c d e f g Le TT, Cramer JP, Chen R, Mayhew S (October 2020). "Evolution of the COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (10): 667–68. doi:10.1038/d41573-020-00151-8. PMID 32887942. S2CID 221503034.
  32. ^ a b c Tregoning JS, Russell RF, Kinnear E (March 2018). "Adjuvanted influenza vaccines". Human Vaccines & Immunotherapeutics. 14 (3): 550–64. doi:10.1080/21645515.2017.1415684. PMC 5861793. PMID 29232151.
  33. ^ a b c d Wang J, Peng Y, Xu H, Cui Z, Williams RO (August 2020). "The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation". AAPS PharmSciTech. 21 (6): 225. doi:10.1208/s12249-020-01744-7. PMC 7405756. PMID 32761294.
  34. ^ a b "COVID-19 vaccine tracker (Refresh URL to update)". vac-lshtm.shinyapps.io. London School of Hygiene & Tropical Medicine. 12 July 2021. Retrieved 10 March 2021.
  35. ^ "Approved Vaccines". COVID 19 Vaccine Tracker, McGill University. 12 July 2021.
  36. ^ a b Public Health Agency of Canada, [Agence de la santé publique du Canada] (29 March 2021). "Use of AstraZeneca COVID-19 vaccine in younger adults" (Utilisation du vaccin AstraZeneca contre la COVID-19 chez les jeunes adultes). Government of Canada. Retrieved 2 April 2021.
  37. ^ Greinacher, Andreas; Thiele, Thomas; Warkentin, Theodore E.; Weisser, Karin; Kyrle, Paul A.; Eichinger, Sabine (9 April 2021). "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination". New England Journal of Medicine. 384 (22): 2092–2101. doi:10.1056/NEJMoa2104840. PMC 8095372. PMID 33835769.
  38. ^ Cines, Douglas B.; Bussel, James B. (16 April 2021). "SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia". New England Journal of Medicine. 384 (23): 2254–2256. doi:10.1056/NEJMe2106315. PMC 8063912. PMID 33861524.
  39. ^ Long, Brit; Bridwell, Rachel; Gottlieb, Michael (2021). "Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines". The American Journal of Emergency Medicine. 49: 58–61. doi:10.1016/j.ajem.2021.05.054. ISSN 0735-6757. PMC 8143907. PMID 34062319.
  40. ^ "AstraZeneca COVID-19 Vaccine (AZD1222)" (PDF). ACIP COVID-19 Emergency Meeting. AstraZeneca. 27 January 2021. Retrieved 16 April 2021.
  41. ^ "Vaxzevria (previously COVID-19 Vaccine AstraZeneca): EPAR - Medicine overview (update)". European Medicines Agency (EMA). 12 April 2021 [18 February 2021]. Retrieved 16 April 2021. The name of the vaccine was changed to Vaxzevria on 25 March 2021. Vaxzevria (COVID-19 Vaccine (ChAdOx1-S recombinant) EMA/182334/2021 Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  42. ^ "Serum Institute Of India - ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant) - COVISHIELD". www.seruminstitute.com. Retrieved 16 April 2021.
  43. ^ a b "COVID-19 vaccine safety update: VAXZEVRIA" (PDF). European Medicines Agency. 28 March 2021. Retrieved 31 March 2021.
  44. ^ Marks, Peter. "Joint CDC and FDA Statement on Johnson & Johnson COVID-19 Vaccine". Retrieved 13 April 2021.
  45. ^ Medical Director of AstraZeneca AB (13 April 2021). "Direct healthcare professional communication (DHPC): Vaxzevria (previously COVID-19 Vaccine AstraZeneca): link between the vaccine and the occurrence of thrombosis in combination with thrombocytopenia" (PDF). European Medicines Agency. Retrieved 13 April 2021.
  46. ^ MHRA (1 April 2021). "Research and analysis — Coronavirus vaccine - weekly summary of Yellow Card reporting". gov.UK. Retrieved 3 April 2020.
  47. ^ EMA (2021).
  48. ^ Expert Haematology Panel (7 April 2021). "Guidance produced from the Expert Haematology Panel (EHP) focussed on Covid-19 Vaccine induced Thrombosis and Thrombocytopenia (VITT)" (PDF). BSH.org.uk. British Society for Haematology. Retrieved 15 April 2021.
  49. ^ Nazy, Ishac; Sachs, Ulrich J; Arnold, Donald M.; McKenzie, Steven E; Choi, Phil; Althaus, Karina; Ahlen, Maria Therese; Sharma, Ruchika; Grace, Rachael F; Bakchoul, Tamam (22 April 2021). "Recommendations for the clinical and laboratory diagnosis of vaccine‐induced immune thrombotic thrombocytopenia (VITT) for SARS‐CoV‐2 infections: Communication from the ISTH SSC Subcommittee on Platelet Immunology". Journal of Thrombosis and Haemostasis. Online first (6): 1585–1588. doi:10.1111/jth.15341. PMC 8250233. PMID 34018298.
  50. ^ Flanagan KL, Best E, Crawford NW, Giles M, Koirala A, Macartney K, et al. (2020). "Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines". Frontiers in Immunology. 11: 579250. doi:10.3389/fimmu.2020.579250. PMC 7566192. PMID 33123165.
  51. ^ a b "COVID-19 vaccine tracker (Refresh URL to update)". vac-lshtm.shinyapps.io. London School of Hygiene & Tropical Medicine. 12 July 2021. Retrieved 10 March 2021.
  52. ^ Arbeitman, Claudia R.; Rojas, Pablo; Ojeda-May, Pedro; Garcia, Martin E. (December 2021). "The SARS-CoV-2 spike protein is vulnerable to moderate electric fields". Nature Communications. 12 (1): 5407. doi:10.1038/s41467-021-25478-7.
  53. ^ a b c d Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, Mayhew S (May 2020). "The COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (5): 305–06. doi:10.1038/d41573-020-00073-5. PMID 32273591.
  54. ^ a b c Diamond MS, Pierson TC (May 2020). "The Challenges of Vaccine Development against a New Virus during a Pandemic". Cell Host & Microbe. 27 (5): 699–703. doi:10.1016/j.chom.2020.04.021. PMC 7219397. PMID 32407708.
  55. ^ Cross R (29 September 2020). "The tiny tweak behind COVID-19 vaccines". Chemical & Engineering News. 98 (38).
  56. ^ Krammer F (October 2020). "SARS-CoV-2 vaccines in development". Nature. 586 (7830): 516–27. Bibcode:2020Natur.586..516K. doi:10.1038/s41586-020-2798-3. PMID 32967006. S2CID 221887746.
  57. ^ Park KS, Sun X, Aikins ME, Moon JJ (February 2021). "Non-viral COVID-19 vaccine delivery systems". Advanced Drug Delivery Reviews. 169: 137–51. doi:10.1016/j.addr.2020.12.008. PMC 7744276. PMID 33340620.
  58. ^ Kowalski PS, Rudra A, Miao L, Anderson DG (April 2019). "Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery". Molecular Therapy. 27 (4): 710–28. doi:10.1016/j.ymthe.2019.02.012. PMC 6453548. PMID 30846391.
  59. ^ Verbeke R, Lentacker I, De Smedt SC, Dewitte H (October 2019). "Three decades of messenger RNA vaccine development". Nano Today. 28: 100766. doi:10.1016/j.nantod.2019.100766.
  60. ^ "COVID-19 ACIP Vaccine Recommendations". U.S. Centers for Disease Control and Prevention (CDC). Retrieved 18 February 2021.
  61. ^ "Safe COVID-19 vaccines for Europeans". European Commission – European Commission. Retrieved 19 February 2021.
  62. ^ "Regulatory Decision Summary – Pfizer–BioNTech COVID-19 Vaccine". Health Canada, Government of Canada. 9 December 2020. Retrieved 9 December 2020.
  63. ^ "Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Adults". ClinicalTrials.gov. 30 April 2020. NCT04368728. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  64. ^ "A Multi-site Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety and Immunogenicity of four Prophylactic SARS-CoV-2 RNA Vaccines Against COVID-19 Using Different Dosing Regimens in Healthy Adults". EU Clinical Trials Register. European Union. 14 April 2020. EudraCT 2020-001038-36. Archived from the original on 22 April 2020. Retrieved 22 April 2020.
  65. ^ "A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19". ClinicalTrials.gov. 14 July 2020. NCT04470427. Archived from the original on 11 October 2020. Retrieved 27 July 2020.
  66. ^ Palca J (27 July 2020). "COVID-19 vaccine candidate heads to widespread testing in U.S." NPR. Archived from the original on 11 October 2020. Retrieved 27 July 2020.
  67. ^ "CureVac Final Data from Phase 2b/3 Trial of First-Generation COVID-19 Vaccine Candidate, CVnCoV, Demonstrates Protection in Age Group of 18 to 60". CureVac (Press release). 30 June 2021. Retrieved 2 July 2021.
  68. ^ a b c Moghimi SM (March 2021). "Allergic Reactions and Anaphylaxis to LNP-Based COVID-19 Vaccines". Molecular Therapy. 29 (3): 898–900. doi:10.1016/j.ymthe.2021.01.030. PMC 7862013. PMID 33571463.
  69. ^ a b "What are viral vector-based vaccines and how could they be used against COVID-19?". Gavi, the Vaccine Alliance (GAVI). 2020. Retrieved 26 January 2021.
  70. ^ "Understanding Viral Vector COVID-19 Vaccines". U.S. Centers for Disease Control and Prevention (CDC). 13 April 2021. Retrieved 19 April 2021.
  71. ^ "Investigating a Vaccine Against COVID-19". ClinicalTrials.gov. 26 May 2020. NCT04400838. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  72. ^ "A Phase 2/3 study to determine the efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19". EU Clinical Trials Register. European Union. 21 April 2020. EudraCT 2020-001228-32. Archived from the original on 5 October 2020. Retrieved 3 August 2020.
  73. ^ O'Reilly P (26 May 2020). "A Phase III study to investigate a vaccine against COVID-19". ISRCTN. doi:10.1186/ISRCTN89951424. ISRCTN89951424.
  74. ^ Corum J, Carl Z (8 January 2021). "How Gamaleya's Vaccine Works". The New York Times. Retrieved 27 January 2021.
  75. ^ "A Study of Ad26.COV2.S in Adults". 4 August 2020. Archived from the original on 16 September 2020. Retrieved 23 August 2020.
  76. ^ "A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants". US National Library of Medicine. Archived from the original on 26 September 2020.
  77. ^ Johnson C, McGinley L. "Johnson & Johnson seeks emergency FDA authorization for single-shot coronavirus vaccine". The Washington Post.
  78. ^ "It's not just Johnson & Johnson: China has a single-dose COVID-19 vaccine that's 65% effective". Fortune. Retrieved 28 February 2021.
  79. ^ Wu S, Zhong G, Zhang J, Shuai L, Zhang Z, Wen Z, et al. (August 2020). "A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge". Nat Commun. 11 (1): 4081. Bibcode:2020NatCo..11.4081W. doi:10.1038/s41467-020-17972-1. PMC 7427994. PMID 32796842.
  80. ^ "Single dose vaccine, Sputnik Light, authorized for use in Russia". sputnikvaccine.com. Retrieved 12 August 2021.
  81. ^ "Introducing a new member of the Sputnik family - a single dose Sputnik Light!". Twitter. Retrieved 12 August 2021.
  82. ^ Petrovsky N, Aguilar JC (October 2004). "Vaccine adjuvants: current state and future trends". Immunology and Cell Biology. 82 (5): 488–96. doi:10.1111/j.0818-9641.2004.01272.x. PMID 15479434. S2CID 154670.
  83. ^ "Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of SARS-CoV-2 Infection (COVID-19) (Renqiu)". ClinicalTrials.gov. 12 May 2020. NCT04383574. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  84. ^ "Clinical Trial of Efficacy and Safety of Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine in Healthcare Professionals (PROFISCOV)". ClinicalTrials.gov. 2 July 2020. NCT04456595. Archived from the original on 11 October 2020. Retrieved 3 August 2020.
  85. ^ PT. Bio Farma (10 August 2020). "A Phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-COV-2 inactivated vaccine in healthy adults aged 18–59 years in Indonesia". Registri Penyakit Indonesia. Retrieved 15 August 2020.
  86. ^ Chen W, Al Kaabi N (18 July 2020). "A Phase III clinical trial for inactivated novel coronavirus pneumonia (COVID-19) vaccine (Vero cells)". Chinese Clinical Trial Registry. Retrieved 15 August 2020.
  87. ^ Ivanova P (20 February 2021). "Russia approves its third COVID-19 vaccine, CoviVac". Reuters. Retrieved 11 April 2021.
  88. ^ "Kazakhstan rolls out its own COVID-19 vaccine". Reuters. 27 April 2021. Retrieved 2 July 2021.
  89. ^ "FarsNews Agency Iran Licenses Emergency Injection of Home-Made Anti-Coronavirus Vaccine". www.farsnews.ir. 14 June 2021. Retrieved 25 August 2021.
  90. ^ "VLA2001 COVID-19 Vaccine". Precision Vaccinations. 31 December 2020. Retrieved 11 January 2021.
  91. ^ "Dose Finding Study to Evaluate Safety, Tolerability and Immunogenicity of an Inactiviated Adjuvanted Sars-Cov-2 Virus Vaccine Candidate Against Covid-19 in Healthy Adults". U.S. National Library of Medicine. 30 December 2020. Retrieved 11 January 2021.
  92. ^ "Module 2 – Subunit vaccines". WHO Vaccine Safety Basics.
  93. ^ "Study of the Safety, Reactogenicity and Immunogenicity of "EpiVacCorona" Vaccine for the Prevention of COVID-19 (EpiVacCorona)". ClinicalTrials.gov. 22 September 2020. NCT04368988. Retrieved 16 November 2020.
  94. ^ "MVC COVID-19 Vaccine Obtains Taiwan EUA Approval". www.medigenvac.com. Retrieved 7 August 2021.
  95. ^ "Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrix-M Adjuvant". ClinicalTrials.gov. 30 April 2020. NCT04368988. Archived from the original on 14 July 2020. Retrieved 14 July 2020.
  96. ^ "A Study on the Safety, Tolerability and Immune Response of SARS-CoV-2 Sclamp (COVID-19) Vaccine in Healthy Adults". ClinicalTrials.gov. 3 August 2020. NCT04495933. Archived from the original on 11 October 2020. Retrieved 4 August 2020.
  97. ^ "UQ-CSL V451 Vaccine". precisionvaccinations.com. Retrieved 11 December 2020.
  98. ^ a b Mudgal, Rajat; Nehul, Sanketkumar; Tomar, Shailly (15 September 2020). "Prospects for mucosal vaccine: shutting the door on SARS-CoV-2". Human Vaccines and Immunotherapeutics. 16 (12): 2921–2931. doi:10.1080/21645515.2020.1805992. ISSN 2164-5515. PMC 7544966. PMID 32931361.
  99. ^ a b c Rhee, Joon Haeng (2020). "Current and New Approaches for Mucosal Vaccine Delivery". Mucosal Vaccines. Mucosal Vaccines. Elsevier. pp. 325–356. doi:10.1016/b978-0-12-811924-2.00019-5. ISBN 9780128119242. PMC 7149853.
  100. ^ a b c "Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine)". US Centers for Disease Control and Prevention. 3 August 2021. Retrieved 8 September 2021.
  101. ^ "Fluenz Tetra". European Medicines Agency. 9 May 2016. Retrieved 8 September 2021.
  102. ^ "A prospective, randomized, adaptive, phase I/II clinical study to evaluate the safety and immunogenicity of Novel Corona Virus −2019-nCov vaccine candidate of M/s Cadila Healthcare Limited by intradermal route in healthy subjects". ctri.nic.in. Clinical Trials Registry – India. 15 December 2020. CTRI/2020/07/026352. Archived from the original on 22 November 2020.
  103. ^ "Safety, Tolerability and Immunogenicity of INO-4800 for COVID-19 in Healthy Volunteers". ClinicalTrials.gov. 7 April 2020. NCT04336410. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  104. ^ "IVI, INOVIO, and KNIH to partner with CEPI in a Phase I/II clinical trial of INOVIO's COVID-19 DNA vaccine in South Korea". International Vaccine Institute. 16 April 2020. Retrieved 23 April 2020.
  105. ^ "Study of COVID-19 DNA Vaccine (AG0301-COVID19)". ClinicalTrials.gov. 9 July 2020. NCT04463472. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  106. ^ "Safety and Immunogenicity Study of GX-19, a COVID-19 Preventive DNA Vaccine in Healthy Adults". ClinicalTrials.gov. 24 June 2020. NCT04445389. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  107. ^ "S. Korea's Genexine begins human trial of coronavirus vaccine". Reuters. 19 June 2020. Archived from the original on 11 October 2020. Retrieved 25 June 2020.
  108. ^ Chang LJ (9 March 2020). "Safety and Immunity of Covid-19 aAPC Vaccine". ClinicalTrials.gov. NCT04299724. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  109. ^ "Immunity and Safety of Covid-19 Synthetic Minigene Vaccine". ClinicalTrials.gov. 19 February 2020. NCT04276896. Archived from the original on 11 October 2020. Retrieved 14 July 2020.
  110. ^ "A Phase I/II Randomized, Multi-Center, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine (IIBR-100) in Adults". ClinicalTrials.gov. 1 November 2020. NCT04608305.
  111. ^ Johnson CY, Mufson S (11 June 2020). "Can old vaccines from science's medicine cabinet ward off coronavirus?". The Washington Post. ISSN 0190-8286. Retrieved 31 December 2020.
  112. ^ "Bacille Calmette-Guérin (BCG) vaccination and COVID-19". World Health Organization (WHO). 12 April 2020. Archived from the original on 30 April 2020. Retrieved 1 May 2020.
  113. ^ Simpson S, Kaufmann MC, Glozman V, Chakrabarti A (May 2020). "Disease X: accelerating the development of medical countermeasures for the next pandemic". The Lancet. Infectious Diseases. 20 (5): e108–15. doi:10.1016/S1473-3099(20)30123-7. PMC 7158580. PMID 32197097.
  114. ^ a b c d Sanger DE, Kirkpatrick DD, Zimmer C, Thomas K, Wee SL (2 May 2020). "With Pressure Growing, Global Race for a Vaccine Intensifies". The New York Times. ISSN 0362-4331. Archived from the original on 11 May 2020. Retrieved 2 May 2020.
  115. ^ Zabaleta N, Dai W, Bhatt U, Hérate C, Maisonnasse P, Chichester JA, et al. (August 2021). "An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates". Cell Host & Microbe. 29 (9): 1437–1453.e8. doi:10.1016/j.chom.2021.08.002. PMC 8346325. PMID 34428428. S2CID 231676030.
  116. ^ a b c d Steenhuysen J, Eisler P, Martell A, Nebehay S (27 April 2020). "Special Report: Countries, companies risk billions in race for coronavirus vaccine". Reuters. Archived from the original on 15 May 2020. Retrieved 2 May 2020.
  117. ^ Jeong-ho L, Zheng W, Zhou L (26 January 2020). "Chinese scientists race to develop vaccine as coronavirus death toll jumps". South China Morning Post. Archived from the original on 26 January 2020. Retrieved 28 January 2020.
  118. ^ Wee SL (4 May 2020). "China's coronavirus vaccine drive empowers a troubled industry". The New York Times. ISSN 0362-4331. Archived from the original on 4 May 2020. Retrieved 4 May 2020.
  119. ^ Thorp HH (March 2020). "Underpromise, overdeliver". Science. 367 (6485): 1405. Bibcode:2020Sci...367.1405T. doi:10.1126/science.abb8492. PMID 32205459.
  120. ^ Blackwell T (20 April 2020). "COVID-19 vaccine researchers say pandemic lockdown placing many serious obstacles to their work". National Post. Archived from the original on 23 April 2020. Retrieved 3 May 2020.
  121. ^ Chen J (4 May 2020). "Covid-19 has shuttered labs. It could put a generation of researchers at risk". Stat. Archived from the original on 6 May 2020. Retrieved 4 May 2020.
  122. ^ "Vaccine Safety – Vaccines". US Department of Health and Human Services. Archived from the original on 22 April 2020. Retrieved 13 April 2020.
  123. ^ "The drug development process". U.S. Food and Drug Administration (FDA). 4 January 2018. Archived from the original on 22 February 2020. Retrieved 12 April 2020.
  124. ^ Cohen J (June 2020). "Pandemic vaccines are about to face the real test". Science. 368 (6497): 1295–96. Bibcode:2020Sci...368.1295C. doi:10.1126/science.368.6497.1295. PMID 32554572.
  125. ^ Dubé E, Laberge C, Guay M, Bramadat P, Roy R, Bettinger J (August 2013). "Vaccine hesitancy: an overview". Human Vaccines & Immunotherapeutics. 9 (8): 1763–73. doi:10.4161/hv.24657. PMC 3906279. PMID 23584253.
  126. ^ Howard J, Stracqualursi V (18 June 2020). "Fauci warns of 'anti-science bias' being a problem in US". CNN. Archived from the original on 21 June 2020. Retrieved 21 June 2020.
  127. ^ "Vaccines: The Emergency Authorisation Procedure". European Medicines Agency (EMA). 2020. Archived from the original on 24 September 2020. Retrieved 21 August 2020.
  128. ^ Byrne J (19 October 2020). "Moderna COVID-19 vaccine under rolling review process in Canada, EU". BioPharma-Reporter.com, William Reed Business Media Ltd. Retrieved 25 November 2020.
  129. ^ Dangerfield K (20 November 2020). "Pfizer files for emergency use of coronavirus vaccine in U.S. – what about in Canada?". Global News. Retrieved 25 November 2020.
  130. ^ "G20 launches initiative for health tools needed to combat the coronavirus". The Globe and Mail. 25 April 2020.
  131. ^ "Access to COVID-19 Tools (ACT) Accelerator" (PDF). World Health Organization (WHO). 24 April 2020.
  132. ^ "The ACT-Accelerator: frequently asked questions (FAQ)". World Health Organization (WHO). 2020. Retrieved 16 December 2020.
  133. ^ "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization (WHO). 27 April 2020. Archived from the original on 30 April 2020. Retrieved 2 May 2020. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable. To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. [The] WHO is working to ensure that all of them have the chance of being tested at the initial stage of development. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale.
  134. ^ Abedi M (23 March 2020). "Canada to spend $192M on developing COVID-19 vaccine". Global News. Archived from the original on 9 April 2020. Retrieved 24 March 2020.
  135. ^ "Government of Canada's research response to COVID-19". Government of Canada. 23 April 2020. Archived from the original on 13 May 2020. Retrieved 4 May 2020.
  136. ^ Takada N, Satake M (2 May 2020). "US and China unleash wallets in race for coronavirus vaccine". Nikkei Asian Review. Archived from the original on 10 May 2020. Retrieved 3 May 2020.
  137. ^ Morriss E (22 April 2020). "Government launches coronavirus vaccine taskforce as human clinical trials start". Pharmafield. Archived from the original on 17 June 2020. Retrieved 3 May 2020.
  138. ^ Kuznia R, Polglase K, Mezzofiore G (1 May 2020). "In quest for vaccine, US makes 'big bet' on company with unproven technology". CNN. Archived from the original on 13 May 2020. Retrieved 2 May 2020.
  139. ^ Cohen J (May 2020). "U.S. 'Warp Speed' vaccine effort comes out of the shadows". Science. 368 (6492): 692–93. Bibcode:2020Sci...368..692C. doi:10.1126/science.368.6492.692. PMID 32409451.
  140. ^ Sink J, Fabian J, Griffin R (15 May 2020). "Trump introduces 'Warp Speed' leaders to hasten COVID-19 vaccine". Bloomberg. Archived from the original on 21 May 2020. Retrieved 15 May 2020.
  141. ^ LaHucik K (17 June 2021). "U.S. injects $3B-plus into COVID-19 research to develop antiviral pill within a year". Fierce Biotech. Retrieved 11 July 2021.
  142. ^ "World Health Organization timeline – COVID-19". World Health Organization (WHO). 27 April 2020. Archived from the original on 29 April 2020. Retrieved 2 May 2020.
  143. ^ a b c Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, Mayhew S (May 2020). "The COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (5): 305–306. doi:10.1038/d41573-020-00073-5. PMID 32273591.
  144. ^ a b Gates B (February 2020). "Responding to Covid-19: A once-in-a-century pandemic?". The New England Journal of Medicine. 382 (18): 1677–79. doi:10.1056/nejmp2003762. PMID 32109012.
  145. ^ Fauci AS, Lane HC, Redfield RR (March 2020). "Covid-19: Navigating the uncharted". The New England Journal of Medicine. 382 (13): 1268–69. doi:10.1056/nejme2002387. PMC 7121221. PMID 32109011.
  146. ^ a b Le TT, Cramer JP, Chen R, Mayhew S (October 2020). "Evolution of the COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (10): 667–668. doi:10.1038/d41573-020-00151-8. PMID 32887942. S2CID 221503034.
  147. ^ Weintraub R, Yadav P, Berkley S (2 April 2020). "A COVID-19 vaccine will need equitable, global distribution". Harvard Business Review. ISSN 0017-8012. Archived from the original on 9 June 2020. Retrieved 9 June 2020.
  148. ^ "COVID-19 pandemic reveals the risks of relying on private sector for life-saving vaccines, says expert". CBC Radio. 8 May 2020. Archived from the original on 13 May 2020. Retrieved 8 June 2020.
  149. ^ Ahmed DD (4 June 2020). "Oxford, AstraZeneca COVID-19 deal reinforces 'vaccine sovereignty'". Stat. Archived from the original on 12 June 2020. Retrieved 8 June 2020.
  150. ^ Grenfell R, Drew T (14 February 2020). "Here's why the WHO says a coronavirus vaccine is 18 months away". Business Insider. Retrieved 11 November 2020.
  151. ^ Offit, Paul. "TWiV 720: With vaccines, Offit is on it". This Week in Virology Podcast. Vincent Racaniello Youtube Channel. Retrieved 14 July 2021.
  152. ^ "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization (WHO). 27 April 2020. Archived from the original on 30 April 2020. Retrieved 2 May 2020. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable. To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. [The] WHO is working to ensure that all of them have the chance of being tested at the initial stage of development. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale.
  153. ^ Yamey G, Schäferhoff M, Hatchett R, Pate M, Zhao F, McDade KK (May 2020). "Ensuring global access to COVID‑19 vaccines". Lancet. 395 (10234): 1405–06. doi:10.1016/S0140-6736(20)30763-7. PMC 7271264. PMID 32243778. CEPI estimates that developing up to three vaccines in the next 12–18 months will require an investment of at least US$2 billion. This estimate includes Phase 1 clinical trials of eight vaccine candidates, progression of up to six candidates through Phase 2 and 3 trials, completion of regulatory and quality requirements for at least three vaccines, and enhancing global manufacturing capacity for three vaccines.
  154. ^ "WHO 'backed China's emergency use' of experimental Covid-19 vaccines". South China Morning Post. 25 September 2020. Archived from the original on 26 September 2020. Retrieved 26 September 2020.
  155. ^ Kramer AE (19 September 2020). "Russia Is Slow to Administer Virus Vaccine Despite Kremlin's Approval". The New York Times. ISSN 0362-4331. Archived from the original on 27 September 2020. Retrieved 28 September 2020.
  156. ^ "Pfizer and BioNTech to Submit Emergency Use Authorization Request Today to the U.S. FDA for COVID-19 Vaccine". Pfizer (Press release). 20 November 2020. Retrieved 20 November 2020.
  157. ^ Park A (20 November 2020). "Exclusive: Pfizer CEO Discusses Submitting the First COVID-19 Vaccine Clearance Request to the FDA". Time. Retrieved 20 November 2020.
  158. ^ "Information for Healthcare Professionals on Pfizer/BioNTech COVID-19 vaccine". Medicines & Healthcare products Regulatory Agency (MHRA). 8 December 2020. Retrieved 13 December 2020.
  159. ^ "Conditions of Authorisation for Pfizer/BioNTech COVID-19 vaccine". Medicines and Healthcare products Regulatory Agency (MHRA). 3 December 2020. Retrieved 19 December 2020.
  160. ^ "UK medicines regulator gives approval for first UK COVID-19 vaccine". Medicines and Healthcare Products Regulatory Agency, Government of the UK. 2 December 2020. Retrieved 2 December 2020.<