COVID-19 vaccine

For vaccine development and distribution, see History of COVID-19 vaccine development and Deployment of COVID-19 vaccines.

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 technologies during early 2020. 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. The COVID‑19 vaccines are widely credited for their role in reducing the spread, severity, and death caused by COVID-19.

In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of June 2021[update], 19 vaccines are authorized by at least one national regulatory authority for public use: two RNA vaccines (Pfizer–BioNTech and Moderna), nine conventional inactivated vaccines (BBIBP-CorV, Chinese Academy of Medical Sciences, CoronaVac, Covaxin, CoviVac, COVIran Barakat, Minhai-Kangtai, QazVac, and WIBP-CorV), five viral vector vaccines (Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Johnson & Johnson), and three protein subunit vaccines (EpiVacCorona, Soberana 02, and RBD-Dimer). In total, as of March 2021[update], 308 vaccine candidates are in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.

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. Single dose interim use is under consideration to extend vaccination to as many people as possible until vaccine availability improves.

As of 3 July 2021[update], 3.19 billion doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies. AstraZeneca anticipates producing 3 billion doses in 2021, Pfizer–BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidecia 500 million doses in 2021. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world's population.

## Background

File:Facts about COVID-19 vaccines (English).pdf

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. 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. 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 and MERS 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. As of 2020, there is no cure or protective vaccine proven to be safe and effective against SARS in humans. There is also no proven vaccine against MERS. 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. As of March 2020, there was one (DNA-based) MERS vaccine which completed Phase I clinical trials in humans, and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).

## Vaccine types

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. 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. 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.

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. Several of the synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an immune response to the virus before it attaches to a human cell. 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.

### RNA vaccines

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.

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

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

### 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. 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.

As of January 2021[update], authorized vaccines of this type are the Oxford–AstraZeneca COVID-19 vaccine, the Sputnik V COVID-19 vaccine, Convidecia, and the Johnson & Johnson COVID-19 vaccine.

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

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

### 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.

As of January 2021, authorized vaccines of this type are the Chinese CoronaVac, BBIBP-CorV, and WIBP-CorV; the Indian Covaxin; later this year the Russian CoviVac; and the Kazakhstani vaccine QazVac. Vaccines in clinical trials include the Valneva COVID-19 vaccine.

### 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.

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

### Other types

Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines, at least two lentivirus vector vaccines, a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.

Oral vaccines and intranasal vaccines are being developed and studied.

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

## Formulation

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

## Planning and development

Main articles: History of COVID-19 vaccine development
Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.

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.

### 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.

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. As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020, 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.

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. Additionally, research at universities is obstructed by physical distancing and closing of laboratories.

Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels and adverse effects of the candidate vaccine. 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. Clinical trial organizers also may encounter people unwilling to be vaccinated due to vaccine hesitancy or disbelief in the science of the vaccine technology and its ability to prevent infection. 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.

### Organizations

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

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, and to support clinical trials and develop manufacturing and supply chains for vaccines.

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. Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing.

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.

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. In May 2020, the government announced funding for a fast-track program called Operation Warp Speed.

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.

### History

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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.

## 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. A Phase I–II trial consists of preliminary safety and immunogenicity testing, is typically randomized, placebo-controlled, while determining more precise, effective doses. 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. 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.

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. 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.

### List of authorized and approved vaccines

Further information: List of COVID-19 vaccine authorizations
National regulatory authorities have granted emergency use authorizations for fifteen vaccines. Six of those have been approved for emergency or full use by at least one WHO-recognized stringent regulatory authority. Biologic License Applications for the Pfizer–BioNTech and Moderna COVID-19 vaccines have been submitted to the US Food and Drug Administration (FDA).

RNA vaccines
  Pfizer–BioNTech

  ModernaAdenovirus vector vaccines
  Sputnik V
  Oxford–AstraZeneca
  Johnson & Johnson
  Convidecia

  Sputnik LightInactivated virus vaccines
  Sinopharm (BBIBP)
  CoronaVac
  Covaxin
  Sinopharm (WIBP)
  CoviVac

  QazVacProtein subunit vaccines
  EpiVacCorona

  RBD-Dimer

### Vaccine candidates in human trials

1. ↑ Serum Institute of India will be producing the *ChAdOx1 nCoV-19* vaccine for India and other low- and middle-income countries.
2. ↑ Oxford name: *ChAdOx1 nCoV-19*. Manufacturing in Brazil to be carried out by Oswaldo Cruz Foundation.
3. ↑ 3.0 3.1 Recommended interval. The second dose of the Pfizer–BioNTech and Moderna vaccines can be administered up to six weeks after the first dose to alleviate a shortage of supplies.
4. ↑ Long-term storage temperature. The Pfizer–BioNTech COVID-19 vaccine can be kept between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use, and between 2 and 8 °C (36 and 46 °F) for up to five days before use.
5. ↑ Storage temperature for the frozen Gam-COVID-Vac formulation. The lyophilised Gam-COVID-Vac-Lyo formulation can be stored at 2-8°C.
6. ↑ Latest Phase with published results.
7. ↑ Virus-like particles grown in *Nicotiana benthamiana*

#### Heterologous prime-boost vaccination

Some experts believe that heterologous prime-boost vaccination courses can boost immunity, and several studies have begun to examine this effect. Despite the absence of clinical data on the efficacy and safety of such heterologous combinations, Canada and several European countries have recommended a heterologous second dose for people who have received the first dose of the Oxford–AstraZeneca vaccine.

In February 2021, the Oxford Vaccine Group launched the Com-COV vaccine trial to investigate heterologous prime-boost courses of different COVID-19 vaccines. As of June 2021, the group is conducting two phase II studies: Com-COV and Com-COV2.

In Com-COV, the two heterologous combinations of the Oxford–AstraZeneca and Pfizer–BioNTech vaccines were compared with the two homologous combinations of the same vaccines, with an interval of 28 or 84 days between doses.

In Com-COV2, the first dose is the Oxford–AstraZeneca vaccine or the Pfizer vaccine, and the second dose is the Moderna vaccine, the Novavax vaccine, or a homologous vaccine equal to the first dose, with an interval of 56 or 84 days between doses.

## Efficacy

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

The vaccine's efficacy may be adversely effected if the arm is held improperly or squeezed so the vaccine is injected subcutaneously instead of into the muscle. The current CDC guidance is to not repeat doses that are administered subcutaneously.

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. 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. 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, with the lower limit of the 95% confidence interval being greater than 30%. Aiming for a realistic population vaccination coverage rate of 75%, and depending on the actual basic reproduction number, the necessary effectiveness of a COVID-19 vaccine is expected to need to be at least 70% to prevent an epidemic and at least 80% to extinguish it without further measures, such as social distancing.

Ranges below are 95% confidence intervals unless indicated otherwise, and all values are for all participants regardless of age, according to the references for each of the trials. By definition, the accuracy of the estimates without an associated confidence interval is unknown publicly. Efficacy against severe COVID-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority. Authorized and approved vaccines have shown the following efficacies:

1. ↑ Mild symptoms: fever, dry cough, fatigue, myalgia, arthralgia, sore throat, diarrhea, nausea, vomiting, headache, anosmia, ageusia, nasal congestion, rhinorrhea, conjunctivitis, skin rash, chills, dizziness. Moderate symptoms: mild pneumonia.
2. ↑ Severe symptoms without hospitalization or death for an individual, are any one of the following severe respiratory symptoms measured at rest on any time during the course of observation (on top of having either pneumonia, deep vein thrombosis, dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °C (100 °F)), that however were not persistent/severe enough to cause hospitalization or death: Any respiratory rate ≥30 breaths/minute, heart rate ≥125 beats/minute, oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg.
3. ↑ Severe symptoms causing hospitalization or death, are those requiring treatment at hospitals or results in deaths: dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °C (100 °F), respiratory failure, kidney failure, multiorgan dysfunction, sepsis, shock.
4. ↑ With twelve weeks or more between doses. For an interval of less than six weeks, the trial found an efficacy ≈55% (33–70%).
5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 A confidence interval was not provided, so it is not possible to know the accuracy of this measurement.
6. ↑ With a four-week interval between doses. Efficacy is "at preventing symptomatic COVID-19".
7. ↑ 7.0 7.1 7.2 COVID-19 symptoms observed in the Pfizer–BioNTech vaccine trials, were only counted as such for vaccinated individuals if they began more than seven days after their second dose, and required presence of a positive RT-PCR test result. Mild/moderate cases required at least oen of the following symptoms and a positive test during, or within 4 days before or after, the symptomatic period: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhoea; or vomiting. Severe cases additionally required at least one of the following symptoms: clinical signs at rest indicative of severe systemic illness (RR ≥30 breaths per minute, HR ≥125 beats per minute, SpO2 ≤93% on room air at sea level, or PaO2/FiO2<300mm Hg); respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation, mechanical ventilation, or ECMO); evidence of shock (SBP <90 mm Hg, DBP <60 mm Hg, or requiring vasopressors); significant acute renal, hepatic, or neurologic dysfunction; admission to an ICU; death.
8. ↑ 8.0 8.1 8.2 8.3 8.4 This measurement is not accurate enough to support the high efficacy because the lower limit of the 95% confidence interval is lower than the minimum of 30%.
9. ↑ 9.0 9.1 9.2 9.3 Moderate cases.
10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 Efficacy reported 28 days post-vaccination for the Johnson & Johnson single shot vaccine. A lower efficacy was found for the vaccinated individuals 14 days post-vaccination.
11. ↑ 11.0 11.1 11.2 11.3 No hospitalizations or deaths were detected 28 days post-vaccination for 19,630 vaccinated individuals in the trials, compared with 16 hospitalizations reported in the placebo group of 19,691 individuals (incidence rate 5.2 per 1000 person-years) and seven COVID-19 related deaths for the same placebo group.
12. ↑ Mild/Moderate COVID-19 symptoms observed in the Moderna vaccine trials, were only counted as such for vaccinated individuals if they began more than 14 days after their second dose, and required presence of a positive RT-PCR test result along with at least two systemic symptoms (fever above 38ºC, chills, myalgia, headache, sore throat, new olfactory and taste disorder) or just one respiratory symptom (cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia).
13. ↑ 13.0 13.1 Severe COVID-19 symptoms observed in the Moderna vaccine trials, were defined as symptoms having met the criteria for mild/moderate symptoms plus any of the following observations: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS, (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure <90 mmHg, diastolic BP <60 mmHg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death. No severe cases were detected for vaccinated individuals in the trials, compared with thirty in the placebo group (incidence rate 9.1 per 1000 person-years).
14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 These Phase III data have not been published or peer reviewed.
15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 No cases detected in trial.

### Effectiveness

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

* In Israel, among the 715,425 individuals vaccinated by the Moderna or Pfizer-BioNTech vaccines during the period 20 December 2020, to 28 January 2021, it was observed for the period starting seven days after the second shot, that only 317 people (0.04%) became sick with mild/moderate Covid-19 symptoms and only 16 people (0.002%) were hospitalized.
* The Pfizer-BioNTech and Moderna Covid-19 vaccines provide highly effective protection, according to a report from the US Centers for Disease Control and Prevention (CDC). Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%.
* 15,121 health care workers from 104 hospitals in England, that all had tested negative for COVID-19 antibodies prior of the study, were followed by RT-PCR tests twice a week from 7 December 2020 to 5 February 2021, during a time when the Alpha variant (lineage B.1.1.7) was in circulation as the dominant variant. The study compared the positive results for the 90.7% vaccinated share of their cohort with the 9.3% unvaccinated share, and found that the Pfizer-BioNTech vaccine reduced all infections (including asymptomatic), by 72% (58-86%) three weeks after the first dose and 86% (76-97%) one week after the second dose.
* A study of the general population in Israel conducted from 17 January to 6 March 2021, during a time when the Alpha variant was in circulation as the dominant variant, found that the Pfizer vaccine reduced asymptomatic COVID-19 infections by 94% and symptomatic COVID-19 infections by 97%.
* A study, among pre-surgical patients across the Mayo Clinic system in the United States, showed that mRNA vaccines were 80% protective against asymptomatic infections.
* A study in England found that a single dose of the Oxford–AstraZeneca COVID-19 vaccine is about 73% (27–90%) effective in people aged 70 and older.

1. ↑ Data collected while the Alpha variant was already dominant.
2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 A confidence interval was not provided, so it is not possible to know the accuracy of this measurement.
3. ↑ 3.0 3.1 3.2 Participants aged 80 and older.
4. ↑ 4.0 4.1 4.2 4.3 No cases detected in study.
5. ↑ 5.0 5.1 5.2 Participants aged 60 to 79.

### Critical coverage

See also: Herd immunity#Vaccination, COVID-19#Immunity
While the most immediate goal of vaccination during a pandemic is to protect individuals from disease, a long-term goal is to eventually eradicate it. To do so, the proportion of the population that must be immunized must be greater than the critical vaccination coverage

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Assuming the same R0 ≈ 2.87, the effectiveness against transmission would have to be greater than 86.9% for a realistic coverage level of 75% or 65.2% for an impossible coverage level of 100%. Less effective vaccines would not be able to eradicate the disease.

As of June 2021, several post-marketing studies have already estimated the effectiveness of some vaccines against asymptomatic infection. Prevention of infection has an impact on slowing transmission (particularly asymptomatic and pre-symptomatic), but the exact extent of this effect is still under investigation.

Some variants of SARS-CoV-2 are more transmissible, showing an increased effective reproduction number, indicating an increased basic reproduction number. Controlling them requires greater vaccine coverage, greater vaccine effectiveness against transmission, or a combination of both.

### Variants

See also: Variants of SARS-CoV-2
The interplay between the SARS-CoV-2 virus and its human hosts was initially natural but is now being altered by the prompt availability of vaccines. The potential emergence of a SARS-CoV-2 variant that is moderately or fully resistant to the antibody response elicited by the current generation of COVID-19 vaccines may necessitate modification of the vaccines. Trials indicate many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19. As of February 2021[update], the US Food and Drug Administration believed that all FDA authorized vaccines remained effective in protecting against circulating strains of SARS-CoV-2.

#### Alpha (lineage B.1.1.7)

Main articles: SARS-CoV-2 Alpha variant
Limited evidence from various preliminary studies reviewed by the WHO have indicated retained efficacy/effectiveness against disease from Alpha with the Oxford–AstraZeneca vaccine, Pfizer–BioNTech and Novavax, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated retained antibody neutralization against Alpha with most of the widely distributed vaccines (Sputnik V, Pfizer–BioNTech, Moderna, CoronaVac, BBIBP-CorV, Covaxin), minimal to moderate reduction with the Oxford–AstraZeneca and no data for other vaccines yet.

In December 2020, a new SARS‑CoV‑2 variant, the Alpha variant or lineage B.1.1.7, was identified in the UK.

Early results suggest protection to the variant from the Pfizer-BioNTech and Moderna vaccines.

One study indicated that the Oxford–AstraZeneca COVID-19 vaccine had an efficacy of 42–89% against Alpha, versus 71–91% against other variants.

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

#### Beta (lineage B.1.351)

Main articles: SARS-CoV-2 Beta variant
Limited evidence from various preliminary studies reviewed by the WHO have indicated reduced efficacy/effectiveness against disease from Beta with the Oxford–AstraZeneca vaccine (possibly substantial), Novavax (moderate), Pfizer–BioNTech and Johnson & Johnson (minimal), with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated possibly reduced antibody neutralization against Beta with most of the widely distributed vaccines (Oxford–AstraZeneca, Sputnik V, Johnson & Johnson, Pfizer–BioNTech, Moderna, Novavax; minimal to substantial reduction) except CoronaVac and BBIBP-CorV (minimal to modest reduction), with no data for other vaccines yet.

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

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

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 variant. 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. On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of about a million doses of the vaccine whilst they examine the data and await advice on how to proceed.

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

#### Gamma (lineage P.1)

Main articles: SARS-CoV-2 Gamma variant
Limited evidence from various preliminary studies reviewed by the WHO have indicated likely retained efficacy/effectiveness against disease from Gamma with CoronaVac and BBIBP-CorV, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated retained antibody neutralization against Gamma with Oxford–AstraZeneca and CoronaVac (no to minimal reduction) and slightly reduced neutralization with Pfizer–BioNTech and Moderna (minimal to moderate reduction), with no data for other vaccines yet.

The Gamma variant or lineage P.1 variant (also known as 20J/501Y.V3), initially identified in Brazil, seems to partially escape vaccination with the Pfizer-BioNTech vaccine.

#### Delta (lineage B.1.617)

Main articles: SARS-CoV-2 Delta variant
Limited evidence from various preliminary studies reviewed by the WHO have indicated likely retained efficacy/effectiveness against disease from Delta with the Oxford–AstraZeneca vaccine and Pfizer–BioNTech, with no data for other vaccines yet. Relevant to how vaccines can end the pandemic by preventing asymptomatic infection, they have also indicated reduced antibody neutralization against Delta with Oxford–AstraZeneca (substantial reduction), Pfizer–BioNTech and Covaxin (modest to moderate reduction), with no data for other vaccines yet.

In October 2020, a new variant was discovered in India, which was named lineage B.1.617. There were very few detections until January 2021, but by April it had spread to at least 20 countries in all continents except Antarctica and South America. Among some 15 defining mutations, it has spike mutations D111D (synonymous), G142D, P681R, E484Q and L452R, the latter two of which may cause it to easily avoid antibodies. The variant has frequently been referred to as a 'Double mutant', even though in this respect it is not unusual. In an update on 15 April 2021, PHE designated lineage B.1.617 as a 'Variant under investigation', VUI-21APR-01. On 6 May 2021, Public Health England escalated lineage B.1.617.2 from a Variant Under Investigation to a Variant of Concern based on an assessment of transmissibility being at least equivalent to the Alpha variant.

## Society and culture

### Distribution

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### Access

Main articles: Deployment of COVID-19 vaccines#Equitable 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.

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."

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. 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.

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

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." Edward Bergmark and Arick Wierson are calling for an global vaccination effort and wrote that the wealthier nations' "me-first" mentality could ultimately backfire, because the spread of the virus in poorer countries would lead to more variants, against which current vaccines could be less effective.

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. On 5 May 2021, the Biden administration announced that it supports waiving intellectual property protections for COVID-19 vaccines. The Members of the European Parliament have backed a motion demanding the temporary lifting of intellectual properties rights for Covid-19 vaccines. 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.

In a meeting in April 2021, the World Health Organization's emergency committee addressed concerns of persistent inequity in the global vaccine distribution. Although 9 percent of the world's population lives in the 29 poorest countries, these countries received only 0.3% of all vaccines administered as of May 2021. Locally, in a Agência Pública article from March 15, 2021, Brazil vaccinated twice more white than black people and noticed the fact that the mortality of COVID-19 is bigger in the black population.

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 SRI, which faced serious supply problems due to increased domestic vaccine needs in India from March to June 2021. Currently, 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.

On July 1 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."

### Preventive measures after vaccination

While vaccines substantially reduce the probability of infection, it is still possible for fully vaccinated people to contract and spread COVID-19. 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.

### 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. The declaration is effective in the United States through 1 October 2024.

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

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. 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.

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. 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.

### Misinformation

Main articles: COVID‑19 misinformation#Vaccines
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Fake vaccines containing salt water have also been administered in some countries.

### Vaccine hesitancy

Main articles: Vaccine hesitancy
Some 10% of the public perceives vaccines as unsafe or unnecessary and refuse vaccination, which increases the risk of further viral spread that could lead to COVID‑19 outbreaks. As of May 2020, estimates from two surveys were that 67% or 80% of people in the U.S. would accept a new vaccination against COVID‑19, with wide disparity by education level, employment status, ethnicity, and geography. In March 2021, 19% of US adults claimed to have been vaccinated while 50% announced plans to get vaccinated.

### Encouragement by public figures and celebrities

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

#### Politicians and heads of state

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

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

#### Musicians

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

#### Actresses and actors

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

#### TV personalities

Martha Stewart, Jonathan Van Ness, Al Roker and Dan Rather released photographs of themselves getting vaccinated and encouraged others to do the same. Stephen Fry also shared a photograph of being vaccinated; he wrote, "It's a wonderful moment, but you feel that it's not only helpful for your own health, but you know that you're likely to be less contagious if you yourself happen to carry it ... It's a symbol of being part of society, part of the group that we all want to protect each other and get this thing over and done with." Sir David Attenborough announced that he has been vaccinated. Dutch TV personality Beau van Erven Dorens got his vaccination on live TV in his late-night talkshow on 3 June 2021.

#### Athletes

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

#### Specific communities

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

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

## Research

A study is investigating the long-lasting protection against SARS-CoV-2 provided by the mRNA vaccines.

## See also

* 2009 swine flu pandemic vaccine
* COVID-19 drug development
* COVID-19 drug repurposing research

## Further reading

* "SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates". *NPJ Vaccines* **6** (1): 28. February 2021. . . . //www.ncbi.nlm.nih.gov/pmc/articles/PMC7900244/.
* ﻿Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry﻿ (Report). U.S. Food and Drug Administration (FDA). June 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19.
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* "Chapter 14a: COVID-19". *Immunisation against infectious disease*. Public Health England. 2020. https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a.
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### Vaccine protocols

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## External links

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* COVID‑19 Vaccine Tracker. Regulatory Affairs Professionals Society (RAPS)
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* M.I.T. Lecture 10: Kizzmekia Corbett, Vaccines" on YouTube
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