COVID-19 vaccine

By Wikipedia Contributors

Hypothetical vaccine against COVID-19

A COVID-19 vaccine is a hypothetical vaccine against coronavirus disease 2019 (COVID‑19). Although no vaccine has completed clinical trials, there are multiple attempts in progress to develop such a vaccine. In February 2020, the World Health Organization (WHO) said it did not expect a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus, to become available in less than 18 months.[1] The Coalition for Epidemic Preparedness Innovations (CEPI) – which is organizing a US$2 billion worldwide fund for rapid investment and development of vaccine candidates[2] – indicated in April that a vaccine may be available under emergency use protocols in less than 12 months or by early 2021.[3] On 4 May 2020, the WHO organized a telethon to raise US$8 billion from forty countries to support rapid development of vaccines to prevent COVID-19 infections,[4] also announcing deployment of an international "Solidarity trial" for simultaneous evaluation of several vaccine candidates reaching Phase II-III clinical trials.[5]

By May, 159 vaccine candidates were in development, with five having been initiated in Phase I–II safety and efficacy studies in human subjects, and seven in Phase I trials.[6][7]

Globally accelerated development

Following detection of a novel coronavirus pneumonia in December 2019,[8] the genetic sequence of COVID-19 was published on 11 January 2020, triggering an urgent international response to prepare for the outbreak and hasten development of a preventative vaccine.[3][9][10] The rapidly growing infection rate of COVID-19 worldwide during early 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines,[5] with four vaccine candidates entering human evaluation in March (see table of clinical trials started in 2020).[3][11]

A vaccine for an infectious disease has never before been produced in less than several years, and no previous vaccine exists for preventing a coronavirus infection.[12] As of April, CEPI estimates that as many as six of the 115 vaccine candidates against COVID-19 should be chosen by international coalitions for development through Phase II–III trials, and three should be streamlined through regulatory and quality assurance for eventual licensing at a total cost of at least US$2 billion.[3][11][12] Another analysis estimates 10 candidates will need simultaneous initial development, before a select few are chosen for the final path to licensing.[12]

The vaccine effort is being prioritized for speed of rigorous clinical evaluation for safety and efficacy, financing, and planning to manufacture billions of doses, and eventual worldwide deployment and equitable access among developed and undeveloped countries.[11][12] WHO, CEPI, and the Gates Foundation are investing finances and organizational resources for the prospect that several vaccines will be needed to prevent continuing COVID-19 infection.[12] The vaccines will require custom formulation, special packaging, transportation, and storage in every one of some 200 countries with infected citizens.[12][13] The WHO estimates a total cost of US$8 billion to develop a suite of three or more vaccines having different technologies and distribution to prevent COVID-19 infections worldwide.[5][14][15]

Among organizations that have formed international alliances to expedite vaccine development and prepare for distribution are:

  • the World Health Organization is facilitating collaboration, accelerated research, and international communications on a scale unprecedented in history, beginning in early May a goal to raise US$8 billion, and implement an Access to COVID-19 Tools Accelerator for global vaccine development[4][14]
  • Coalition for Epidemic Preparedness Innovations (CEPI) is working with global health authorities and vaccine developers to raise US$8 billion in a global partnership between public, private, philanthropic, and civil society organizations for accelerated research and clinical testing of eight vaccine candidates, with the 2020-21 goal of supporting three candidates for full development to licensing[3][11][15] The United Kingdom, Canada, Belgium, Norway, Switzerland, Germany and the Netherlands had already donated US$915 million by early May.[4][16]
  • The Gates Foundation, a private charitable organization dedicated to vaccine research and distribution, is donating US$250 million for research and public educational support, mainly in support of CEPI[9][12][13][17]
  • Global Alliance for Vaccines and Immunisation (GAVI) is financing and organizing clinical groups in under-developed countries with COVID-19 vaccination preparedness[12][18]
  • the Global Research Collaboration for Infectious Disease Preparedness (GLoPID-R) works closely with WHO and member states to identify specific funding of research priorities needed for a COVID-19 vaccine, coordinating among the international funding and research organizations to maintain updated information on vaccine progress and avoid duplicate funding[19][20]
  • the International Severe Acute Respiratory and Emerging Infection Consortium organizes and disseminates clinical information on COVID-19 research to inform public health policy on eventual vaccine distribution[21]

Federal governments dedicating resources for national or international investments include:

  • Canada: Between March and late-April, the Canadian government announced CA$275 million in funding for 96 research vaccine research projects at Canadian companies and universities, with plans to establish a "vaccine bank" of several new vaccines that could be used if another coronavirus outbreak occurs.[22][23] A further investment of CA$1.1 billion was added to support clinical trials in Canada and develop manufacturing and supply chains for vaccines.[20] On 4 May, the Canadian government committed CA$850 million to the WHO live streaming effort to raise US$8 billion for COVID-19 vaccines and preparedness.[24]
  • China: The government is providing low-rate loans to vaccine developers through its central bank, and enabled land transfers to build production plants.[16] There are nine Chinese COVID-19 vaccines in development, involving 1,000 scientists and Chinese research institutes and military hospitals.[13] Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing the most promising vaccine candidates, while prioritizing rapid evidence of efficacy over safety.[25] On 18 May, China pledged US$2 billion to support overall efforts by the WHO for programs against COVID-19.[26]
  • European Union: In France, CEPI announced a US$4.9 million investment in a COVID-19 vaccine research consortium involving the Institut Pasteur, Themis Bioscience (Vienna, Austria), and the University of Pittsburgh, bringing CEPI's total investment in COVID-19 vaccine development to US$480 million by May.[27][28] In March, the European Commission provided an 80 million investment in CureVac, a German biotechnology company, to develop a mRNA vaccine.[29] Belgium, Norway, Switzerland, Germany, and the Netherlands have been major contributors to the CEPI effort for COVID-19 vaccine research in Europe.[16]
  • United Kingdom: In April, the UK government formed a COVID-19 vaccine taskforce to stimulate British efforts for rapidly developing a vaccine through collaborations of industry, universities, and government agencies across the vaccine development pipeline, including for clinical trial placement at UK hospitals, regulations for approval, and eventual manufacturing.[30] The vaccine development initiatives at the University of Oxford and Imperial College of London were financed with £44 million in April.[31][32]
  • United States: Biomedical Advanced Research and Development Authority (BARDA) a federal agency that funds disease-fighting technology, announced investments of nearly US$1 billion to support American COVID-19 vaccine development, and preparation for manufacturing the most promising candidates. BARDA made a US$483 million investment in the vaccine developer, Moderna and its partner, Johnson & Johnson.[16][33] BARDA has an additional US$4 billion to spend on vaccine development, and will have roles in other American investment for development of six to eight vaccine candidates to be in clinical studies over 2020-21 by companies, such as Sanofi Pasteur and Regeneron.[33][34]

Partnerships and competition

WHO Solidarity trial

The WHO has developed a multinational coalition of vaccine scientists defining a Global Target Product Profile (TPP) for COVID-19, identifying favorable attributes of safe and effective vaccines under two broad categories: "vaccines for the long-term protection of people at higher risk of COVID-19, such as healthcare workers", and other vaccines to provide rapid-response immunity for new outbreaks.[5] The international TPP team was formed to 1) assess the development of the most promising candidate vaccines; 2) map candidate vaccines and their clinical trial worldwide, publishing a frequently-updated "landscape" of vaccines in development;[35] 3) rapidly evaluate and screen for the most promising candidate vaccines simultaneously before they are tested in humans; and 4) design and coordinate a multiple-site, international randomized controlled trial  – the Solidarity trial for vaccines[5][36]  – to enable simultaneous evaluation of the benefits and risks of different vaccine candidates under clinical trials in countries where there are high rates of COVID-19 disease, ensuring fast interpretation and sharing of results around the world.[5] 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.[5]

Adaptive design for the Solidarity trial

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.[37][38] The WHO Solidarity trial of multiple vaccines in clinical studies during 2020 will apply adaptive design to rapidly alter trial parameters across all study sites as results emerge.[36] Candidate vaccines may be added to the Solidarity trial as they become available if priority criteria are met, while vaccine candidates showing poor evidence of safety or efficacy compared to placebo or other vaccines will be dropped from the international trial.[36]

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.[36][37]

Partnerships, competition, and distribution

Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), among others, are forming alliances with biotechnology companies, national governments, and universities to accelerate progression to an effective vaccine.[13][16] To combine financial and manufacturing capabilities for a pandemic adjuvant technology, GSK joined with Sanofi in an uncommon partnership of multinational companies to support accelerated vaccine development.[39]

During a pandemic on the rapid timeline and scale of COVID-19 infections during 2020, international organizations like WHO and CEPI, vaccine developers, governments and industry are evaluating distribution of the eventual vaccine(s).[5] Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country.[9][12][16] Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need.[9][12][16] Under their agreement with AstraZeneca, the University of Oxford vaccine development team and UK government agreed that UK citizens would not get preferential access to a new COVID-19 vaccine developed by the taxpayer-funded university, but rather consented to having a licensed vaccine distributed multinationally in cooperation with WHO.[31] Several companies plan to initially manufacture a vaccine at low cost, then increase costs for profitability later if annual vaccinations are needed and countries build stock for future needs.[16]

The WHO and CEPI are developing financial resources and guidelines for global deployment of three or more safe, effective COVID-19 vaccines, recognizing the need is different across countries and population segments.[3][5][11][36] For example, successful COVID-19 vaccines would likely be allocated first to healthcare personnel and populations at greatest risk of severe illness and death from COVID-19 infection, such as the elderly or densely-populated impoverished people.[11][40] Both WHO and CEPI discuss concerns that affluent countries should not have priority access to the global supply of eventual COVID-19 vaccines.[3][11][40]

Compressed timelines

Geopolitical issues, safety concerns for vulnerable populations, and manufacturing challenges for producing billions of doses are compressing schedules to shorten the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process typically conducted sequentially over years.[13] As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020,[41] 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.[13][42]

COVID-19: Vaccine technology platforms
May 2020
Molecular platform Total number of candidates

(159 from combined sources[6][7])

Number of candidates in human trials
(^ in Phase II)
Non-replicating viral vector
2 ^
Inactivated virus
Protein subunit
Replicating viral vector
Virus-like particle
Live attenuated virus
Replicating bacterial vector

In the haste to provide a vaccine on a rapid timeline for the COVID-19 pandemic, developers and governments are accepting a high risk of "short-circuiting" the vaccine development process,[16] with one industry executive saying: "The crisis in the world is so big that each of us will have to take maximum risk now to put this disease to a stop".[16] 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.[12][43] If a vaccine fails in development – data show that 84-90% of vaccine candidates fail (have "attrition") in Phase III clinical trials[3][44] – the investment by a manufacturer in a vaccine candidate may exceed US$1 billion, only to have the vaccine fail to show adequate prevention against the virus, leaving millions of useless doses.[12][13][16] In the case of COVID-19 specifically, a vaccine efficacy of 70% may be enough to stop the pandemic, but if it has only 60% efficacy, outbreaks may continue, and having efficacy of less than 60% will be a failure to stop the virus.[12]

As the pandemic expands during 2020, research at universities is obstructed by physical distancing and closing of laboratories.[45][46] Globally, supplies critical to vaccine research and development are increasingly scarce due to international competition or national sequestration.[25] 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.[13][16]

On 15 May, the U.S. government announced federal funding for a fast-track program called "Operation Warp Speed", which has the goals of placing eight diverse vaccine candidates in clinical trials by the fall of 2020, and manufacturing 300 million doses of a licensed vaccine by January 2021. The project was led by Moncef Slaoui.[47][48]

Technology platforms

In April, CEPI scientists reported that 10 different technology platforms were under research and development during early 2020 to create an effective vaccine against COVID‑19.[3] According to CEPI, the platforms based on DNA or messenger RNA offer considerable promise to alter COVID‑19 antigen functions for strong immune responses, and can be rapidly assessed, refined for long-term stability, and prepared for large-scale production capacity.[3] Other platforms being developed in 2020 focus on peptides, recombinant proteins, live attenuated viruses, and inactivated viruses.[3]

In general, the vaccine technologies being developed for COVID‑19 are not like vaccines already in use to prevent influenza, but rather are using "next-generation" strategies for precision on the COVID‑19 infection mechanisms, while hastening development for eventually preventing infection with a new vaccine.[3] Vaccine platforms in development are also designed to address mechanisms for infection susceptibility to COVID‑19 in specific population subgroups, such as the elderly, children, pregnant women, or people with existing weakened immune systems.[3]

Vaccine candidates

CEPI classifies development stages for vaccines as either "exploratory" (planning and designing a candidate, having no evaluation in vivo), "preclinical" (in vivo evaluation with preparation for manufacturing a compound to test in humans), or initiation of Phase I safety studies in healthy people.[3]

Some 159 total vaccine candidates are in early stages of development as either confirmed active projects or in "exploratory" or "preclinical" development, as of mid-May.[3][5][6][7]

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.[49][50] A Phase I–II trial conducts preliminary safety and immunogenicity testing, is typically randomized, placebo-controlled, and at multiple sites, while determining more precise, effective doses.[50] Phase III trials typically involve more participants, including a control group, and test effectiveness of the vaccine to prevent the disease, while monitoring for adverse effects at the optimal dose.[49][50]

Clinical trials started in 2020

COVID‑19: candidate vaccines in Phase I–II trials
Vaccine candidate


Technology Phase of trial


Location Duration References

and notes


(CanSino Biologics, Institute of Biotechnology of the Academy of Military Medical Sciences)

recombinant adenovirus type 5 vector Phase II interventional trial for dosing and side effects (500) China March 2020 to December 2020 [51][52]

(CanSino Biologics, Institute of Biotechnology of the Academy of Military Medical Sciences)

recombinant adenovirus type 5 vector Phase I (108) China March 2020 to December 2020 [3][53] announced on 10 April that will move into Phase II "soon"[51]
ChAdOx1 nCoV-19

(University of Oxford)

adenovirus vector Phase I–II, randomized, placebo-controlled, multiple sites (1000) United Kingdom April 2020 to May 2021 [54][55]
BNT162 (a1, b1, b2, c2)

(BioNTech, Fosun Pharma, Pfizer)

RNA Phase I–II of four vaccines, randomized, placebo-controlled, dose-finding, vaccine candidate-selection (7600) Germany
United States
April 2020 to May 2021 [56][57][58]

(Sinovac Biotech)

inactivated SARS-CoV-2 virus Phase I–II randomized, double-blinded, single-center, placebo-controlled in Xuzhou (744); Phase I–II in Renqiu (422) China April 2020 to December 2020 in Xuzhou; May to July 2020 in Renqiu [59][60]

(Inovio Pharmaceuticals, CEPI, Korea National Institute of Health, International Vaccine Institute)

DNA plasmid delivered by electroporation Phase I–II (40) United States
South Korea
April 2020 to November 2020 South Korean Phase I–II in parallel with Phase I in the U.S.[61][62]

(Moderna, US National Institute of Allergy and Infectious Diseases)

lipid nanoparticle dispersion containing messenger RNA Phase I (45) United States March 2020 to Spring-Summer 2021 [3][63][64]

(Shenzhen Geno-Immune Medical Institute)

lentiviral vector, pathogen-specific artificial antigen presenting dendritic cells Phase I (100) China March 2020 to 2023 [3][65]

(Shenzhen Geno-Immune Medical Institute)

lentiviral minigene vaccine, dendritic cells modified with lentiviral vector Phase I (100) China March 2020 to 2023 [3][66]

(Symvivo Corporation, University of British Columbia, Dalhousie University)

DNA, bacterial medium (oral) Phase I (84) Canada April 2020 to December 2021 [67]

(Beijing Institute of Biological Products, Wuhan Institute of Biological Products)

inactivated COVID-19 virus (vero cells) Phase I (288) China April 2020 to November 2021 has Phase II design registered for > 1000 participants, including children, not yet recruiting[68][69]


SARS-CoV-2 recombinant spike protein nanoparticle with adjuvant Phase I (131) Australia May 2020 to July 2021 [70]
COVID-19: candidate vaccines scheduled for Phase I trials in 2020
Vaccine candidate


Technology Start date announced

(IMV, Inc.,
Canadian Immunization Research Network)

protein subunit, lipid-based delivery mid-2020

(University of Pittsburgh)

protein subunit, microneedle arrays mid-2020

(University of Cambridge)

protein subunit, S protein mid-2020

(Imperial College London)

RNA; saRNA mid-2020


RNA, mRNA mid-2020

(Arcturus Therapeutics,
Duke University-National University of Singapore)

RNA, mRNA mid-2020

(Sanofi Pasteur, GlaxoSmithKline)

protein subunit, S protein mid-2020

(Cobra Biologics, Karolinska Institute)

DNA plasmid mid-2020

(Generex Biotech)

synthetic viral peptides combined with Ii-key immune activation mid-2020

(Clover Biopharm)

fragments of the SARS-CoV-2 spike protein mid-2020

(Medicago, Inc.)

plant-derived virus-like particle July–August

(Janssen; Beth Israel Deaconess Medical Center)

non-replicating viral vector September

(SK Biosciences, Government of Saskatchewan;
Korea Centers for Disease Control and Prevention)

COVID-19 antigen subunits September

(University of Wisconsin-Madison;
FluGen; Bharat Biotech)

self-limiting influenza virus late 2020

(Takis; Applied DNA Sciences; Evvivax)

DNA late 2020

(Altimmune; University of Alabama at Birmingham)

non-replicating viral vector; intranasal late 2020

(Vaxart; Emergent BioSolutions)

non-replicating viral vector; oral late 2020

(VBI Vaccines; National Research Council of Canada)

pan-coronavirus No earlier than December 2020

Preclinical research

In April, the WHO issued a statement representing dozens of vaccine scientists around the world, pledging collaboration to speed development of a vaccine against COVID‑19.[72] The WHO coalition is encouraging international cooperation between organizations developing vaccine candidates, national regulatory and policy agencies, financial contributors, public health associations, and governments for eventual manufacturing of a successful vaccine in quantities sufficient to supply all affected regions, particularly low-resource countries.[3] Industry analysis of vaccine development historically shows failure rates of 84-90%.[3][44]

Because COVID‑19 is a novel virus target with properties still being discovered and requiring innovative vaccine technologies and development strategies, the risks associated with developing a successful vaccine across all steps of preclinical and clinical research are high.[3] To assess potential for vaccine efficacy, unprecedented computer simulations, and new COVID‑19-specific animal models are being developed, but these methods remain untested by unknown characteristics of the COVID‑19 virus, and are being organized multinationally during 2020.[3] Of the confirmed active vaccine candidates, about 70% are being developed by private companies, with the remaining projects under development by academic, government coalitions, and health organizations.[3] Most of the vaccine developers are small firms or university research teams with little experience in successful vaccine design and limited capacity for advanced clinical trial costs and manufacturing without partnership by multinational pharmaceutical companies.[3] The general geographic distribution of COVID‑19 vaccine development involves organizations in the United States and Canada, together having about 46% of the world's active vaccine research, compared with 36% in Asian countries, including China, and 18% in Europe.[3]

In early April, CEPI scientists stated that 115 vaccine candidates were in development as either "exploratory/preclinical" projects or in Phase I safety trials in human participants.[3] The table derives from tracking public sources for progress on emerging vaccine candidates scheduled for Phase I trial starts in 2020.

Scheduled Phase I trials in 2020

Many vaccine candidates under design or preclinical development for COVID‑19 in 2020, will not gain approval for human studies due to toxicity, ineffectiveness to induce immune responses or dosing failures in laboratory animals, or because of underfunding.[73][74] The probability of success for an infectious disease vaccine candidate to pass preclinical barriers and reach Phase I of human testing is 41-57%.[73]

Commitment to first-in-human testing of a vaccine candidate represents a substantial capital cost for vaccine developers, estimated to be from US$14 million to US$25 million for a typical Phase I trial program, but possibly as much as US$70 million.[73][75] For comparison, during the Ebola virus epidemic of 2013-16, there were 37 vaccine candidates in urgent development, but only one eventually succeeded as a licensed vaccine, involving a total cost to confirm efficacy in Phase II–III trials of about US$1 billion.[73]

Non-specific vaccine

Some vaccines have heterologous effects, also called non-specific effects. That means they can have benefits beyond the disease they prevent.[76] The anti-tuberculosis vaccine, BCG vaccine, is an example that is being tested to determine if it has a protective effect against COVID‑19, pursuant to assertions that COVID‑19 mortality was lower in countries having routine BCG vaccine administration.[77] According to the World Health Organization (WHO) there is no evidence that the Bacille Calmette-Guérin vaccine (BCG) protects people against infection with COVID-19 virus.[78]

In March 2020, a randomized trial of BCG vaccine to reduce COVID‑19 illness began in the Netherlands, seeking to recruit 1,000 healthcare workers.[79] A further randomized trial in Australia is seeking to enrol 4,170 healthcare workers.[80][81] A further 700 healthcare workers from Boston and Houston will be recruited in another trial,[82] and 900 healthcare workers in Egypt in a trial registered by a university in Cairo, Egypt.[83] An additional trial in the Netherlands is testing whether BCG vaccine provides protection for older people, recruiting 1,000 people over 65 years and 600 younger adults.[84] A trial of BCG in 1,000 healthcare workers in Medellín, Colombia was registered on 24 April 2020.[85] Other trials of BCG in healthcare workers were registered in late April – early May: 1,100 participants in Brazil,[86] 1,120 in France,[87] 1,500 in Denmark,[88] and 500 in South Africa.[89]

A randomized placebo-controlled trial to test whether measles-mumps-rubella (MMR) vaccine can protect healthcare workers from COVID-19 was scheduled to begin with 200 participants during May in Cairo.[90]

Potential limitations

It is possible vaccines in development will not be safe or effective.[91] One study found that between 2006 and 2015, the success rate of obtaining approval from Phase I to successful Phase III trials was 16.2% for vaccines,[44] and CEPI indicates a potential success rate of only 10% for vaccine candidates in 2020 development.[3]

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.[3] Although the quality and quantity of antibody production by a potential vaccine is intended to neutralize the COVID-19 infection, a vaccine may have unintended effects by causing antibody-dependent disease enhancement (ADE), which is associated with upregulation of proinflammatory cytokine secretion and increased lung pathology.[92] The vaccine technology platform (e.g., viral vector vaccine, spike (S) protein vaccine or protein subunit vaccine, as examples), vaccine dose, timing of repeat vaccinations for the possible recurrence of COVID-19 infection, and elderly age are factors determining the risk and extent of ADE.[92] The antibody response to a vaccine is a variable of vaccine technologies in development, including whether the vaccine has precision in its mechanism, and choice of the route for how it is given (intramuscular, intradermal, oral, or nasal).[92][93]

Early research to assess vaccine efficacy using COVID‑19-specific animal models, such as ACE2-transgenic mice, other laboratory animals, and non-human primates, indicate a need for biosafety-level 3 containment measures for handling live viruses, and international coordination to ensure standardized safety procedures.[3] 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."[3]

While the flu vaccine is typically mass-produced by injecting the virus into the eggs of chickens, this method will not work for the COVID‑19 vaccine, as the SARS-CoV-2 virus cannot replicate inside eggs.[94]

Possibly 10% or more of the public perceives vaccines as unsafe and unnecessary, refusing vaccination ("vaccine hesitancy") and increasing the risk of further COVID-19 outbreaks.[95]

Causes of failure

Vaccine failures occur by three major factors:[93] 1) inadequacies of the vaccine itself resulting from multiple factors, such as incomplete technology efficacy (less than 60% efficacy is failure),[12] ineffective vaccination route of administration (muscle vs. skin, oral, or nasal), or failed cold chain distribution or storage;[93] 2) host-("vaccinee")-related determinants of which a person's genetics, health status (underlying disease, nutrition, pregnancy, sensitivities or allergies), immune competence, age, economic or cultural environment can be primary or secondary factors;[93] and 3) inability of the design and control of clinical trial parameters to determine effectiveness of immunization in the infected population.[96] Elderly (above age 60), allergen-hypersensitive, and obese people have susceptibility to compromised immunogenicity that prevents or inhibits vaccine effectiveness, possibly requiring separate vaccine technologies for these specific populations or repetitive booster vaccinations to limit virus transmission.[93][97]


An effective vaccine for coronavirus could save trillions of dollars in global economic impact, according to one expert, and would therefore make any price tag in the billions look small in comparison.[98] It is not yet known if it is even scientifically possible to create a vaccine for this virus, and it is not yet known exactly how much the vaccine development will cost.[9] It is possible that billions of dollars could be invested without success.[12][13][16]

The European Commission organized and held a video conference of world leaders on May 4, 2020 at which US$8 billion was raised for coronavirus vaccine development.[99]

After the vaccine is invented, billions of doses will need to be manufactured and distributed worldwide. In April 2020, the Gates Foundation estimated that manufacturing and distribution could cost as much as US$25 billion.[100]

Controversy of proposed "challenge" studies

During the global emergency of the COVID‑19 pandemic, strategies are under consideration to fast-track the timeline for licensing a vaccine against COVID‑19, especially by compressing (to a few months) the usually lengthy duration of Phase II–III trials (typically, many years).[101][102][103] Following preliminary proof of safety and efficacy of a candidate vaccine in laboratory animals and healthy humans, controlled "challenge" studies may be implemented to bypass typical Phase III research, providing an accelerated path to license a vaccine for widespread prevention against COVID‑19.[101][104] Challenge studies have been implemented previously for diseases less deadly than COVID‑19 infection, such as common influenza, typhoid fever, cholera, and malaria.[102]

The design of a challenge study involves first, simultaneously testing a vaccine candidate for immunogenicity and safety in laboratory animals and healthy adult volunteers (100 or fewer) – which is usually a sequential process using animals first – and second, rapidly advancing its effective dose into a large-scale Phase II–III trial in previously-uninfected, low-risk volunteers (such as young adults), who would then be deliberately infected with COVID‑19 for comparison with a placebo control group.[101][102][104] Following the challenge, the volunteers would be monitored closely in clinics with life-saving resources, if needed.[101][102] Volunteering for a vaccine challenge study during the COVID‑19 pandemic is likened to the emergency service of healthcare personnel for COVID‑19-infected people, firefighters, or organ donors.[101]

Although challenge studies are ethically questionable due to the unknown hazards for the volunteers of possible COVID‑19 disease enhancement and whether the vaccine received has long-term safety (among other cautions), challenge studies may be the only option available as the COVID‑19 pandemic worsens, according to some infectious disease experts,[101][102][104] to rapidly produce an effective vaccine that will minimize the projected millions of deaths worldwide from COVID‑19 infection.[101][105] The World Health Organization has developed a guidance document of several criteria for conducting challenge studies in healthy people, including scientific and ethical evaluation, public consultation and coordination, selection and informed consent of the participants, and monitoring by independent experts.[106]

Legal status

On 4 February 2020, U.S. Secretary of Health and Human Services Alex Azar published a notice of declaration under the Public Readiness and Emergency Preparedness Act for medical countermeasures against COVID‑19, covering "any vaccine, used to treat, diagnose, cure, prevent, or mitigate COVID‑19, or the transmission of SARS-CoV-2 or a virus mutating therefrom", and stating that the declaration precludes "liability claims alleging negligence by a manufacturer in creating a vaccine, or negligence by a health care provider in prescribing the wrong dose, absent willful misconduct".[107] The declaration is effective in the United States through 1 October 2024.


Vaccines have been produced against several diseases caused by coronaviruses for animal use, including for infectious bronchitis virus in birds, canine coronavirus and feline coronavirus.[108]

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[109] and MERS[110] have been tested in non-human animal models. As of 2020, there is no cure or protective vaccine for SARS that has been shown to be both safe and effective in humans.[111][112] According to research papers 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.[113][114][115]

There is also no proven vaccine against MERS.[116] When MERS became prevalent, it was believed that existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection.[111][117] As of March 2020, there was one (DNA based) MERS vaccine which completed Phase I clinical trials in humans,[118] and three others in progress, all of which are viral-vectored vaccines, two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac), and one MVA-vectored (MVA-MERS-S).[119]


Social media posts have promoted a conspiracy theory claiming the virus behind COVID‑19 was known and that a vaccine was already available. The patents cited by various social media posts reference existing patents for genetic sequences and vaccines for other strains of coronavirus such as the SARS coronavirus.[120][121]

See also


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