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A COVID‑19 vaccine is any of several different vaccines intended to provide acquired immunity against coronavirus disease 2019 (COVID‑19). Previous work to develop a vaccine against the coronavirus diseases SARS and MERS established knowledge about the structure and function of coronaviruses – which accelerated development during early 2020 of varied technology platforms for a COVID‑19 vaccine. As of October 2020, there were 321 vaccine candidates in development, a 2.5 fold increase since April. However, no candidate has completed clinical trials to prove its safety and efficacy. In October, some 42 vaccine candidates were in clinical research: namely 33 in Phase I–II trials and 9 in Phase II–III trials.
The World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), and the Gates Foundation (GF) are committing money and organizational resources for the prospect that several vaccines will be needed to prevent continuing COVID‑19 infection. The CEPI, which is organizing a US$2 billion worldwide fund for rapid investment and development of vaccine candidates, indicated in September that clinical data to support licensure may be available by the end of 2020. On 4 May 2020, the WHO organized a telethon which received US$8.1 billion in pledges from forty countries to support rapid development of vaccines to prevent COVID‑19 infections. At the same time, the WHO also announced the deployment of an international "Solidarity trial" for simultaneous evaluation of several vaccine candidates reaching Phase II–III clinical trials.
Synopsis and history
SARS and MERS
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 may 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 of which are viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac), and one MVA-vectored (MVA-MERS-S).
COVID-19 vaccine development in 2020
A vaccine for an infectious disease has never before been produced in less than several years, and no vaccine exists for preventing a coronavirus infection in humans. After the coronavirus was detected in December 2019, the genetic sequence of COVID‑19 was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten development of a preventive 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. 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, with four vaccine candidates entering human evaluation in March (see the table of clinical trials started in 2020, below).
In April 2020, the WHO estimated a total cost of US$8 billion to develop a suite of three or more vaccines having different technologies and distribution. By April 2020, "almost 80 companies and institutes in 19 countries" were working on this virtual gold rush. Also in April, CEPI estimated that as many as six of the 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. Another analysis estimates 10 candidates will need simultaneous initial development, before a select few are chosen for the final path to licensing.
In July 2020, Anglo-American intelligence and security organisations of the respective governments and armed forces, as the UK's National Cyber Security Centre, together with the Canadian Communications Security Establishment, the United States Department for Homeland Security Cybersecurity Infrastructure Security Agency, and the US National Security Agency (NSA) alleged that Russian state-backed hackers may have been trying to steal COVID-19 treatment and vaccine research from academic and pharmaceutical institutions in other countries; Russia has denied it.
During 2020, major changes in the overall effort of developing COVID-19 vaccines since early in the year have been the increasing number of collaborations of the multinational pharmaceutical industry with national governments, and the diversity and growing number of biotechnology companies in many countries focusing on a COVID-19 vaccine. According to CEPI, the general geographic distribution of COVID‑19 vaccine development involves organizations in North America having about 40% of the world's COVID-19 vaccine research, compared with 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.
Organizations have formed international alliances to expedite vaccine development and prepare for distribution, including the WHO which is facilitating collaboration, accelerated research, and international communications on a scale unprecedented in history, beginning in early May by raising US$8.1 billion in pledges. The WHO also implemented Covid-19 Vaccines Global Access (COVAX) for coordinating global vaccine development, the vaccine pillar of Access to COVID-19 Tools (ACT) Accelerator in collaboration with GAVI and the Coalition for Epidemic Preparedness Innovations (CEPI). In July, the WHO announced that 165 countries, representing up to 60% of the world population, had agreed to a WHO COVAX plan for fair and equitable distribution of an eventual licensed vaccine, assuring that each participating country would receive a guaranteed share of doses to vaccinate the most vulnerable 20% of its population by the end of 2021. COVAX has the goal to accelerate the development and manufacturing of COVID-19 vaccines, and to assure that access to licensed vaccines is equitably provided to all countries.
CEPI is working with international health authorities and vaccine developers to create another US$2 billion fund 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 several candidates for full development to licensing. The United Kingdom, Canada, Belgium, Norway, Switzerland, Germany and the Netherlands had already donated US$915 million to CEPI by early May. The Bill & Melinda Gates Foundation (Gates Foundation), a private charitable organization dedicated to vaccine research and distribution, is donating US$250 million in support of CEPI for research and public educational support on COVID‑19 vaccines.
The Global Research Collaboration for Infectious Disease Preparedness (GLoPID-R) is working closely with the WHO and member states to identify priorities for funding specific researches 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. The International Severe Acute Respiratory and Emerging Infection Consortium is organizing and disseminating clinical information on COVID‑19 research to inform public health policy on eventual vaccine distribution.
On 4 June, a virtual summit was coordinated from London, UK, among private and government representatives of 52 countries, including 35 heads of state from G7 and G20 nations, to raise US$8.8 billion in support of the Global Alliance for Vaccines and Immunisation (GAVI) to prepare for COVID‑19 vaccinations of 300 million children in under-developed countries through 2025. Major contributions were US$1.6 billion from The Gates Foundation and GB£330 million per year over five years by the UK government (approximately US$2.1 billion in June 2020).
National governments dedicating resources for national or international investments in vaccine research, development, and manufacturing beginning in 2020 included the Canadian government which 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. A further investment of CA$1.1 billion was added to support clinical trials in Canada and develop manufacturing and supply chains for vaccines. On 4 May, the Canadian government committed CA$850 million to the WHO's live streaming effort to raise US$8 billion for COVID‑19 vaccines and preparedness.
In China, the government is providing low-rate loans to a vaccine developer through its central bank, and has "quickly made land available for the company" to build production plants. As of June 2020, six of the eleven COVID‑19 vaccine candidates in early-stage human testing were developed by Chinese organizations. 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. On 18 May, China had pledged US$2 billion to support overall efforts by the WHO for programs against COVID‑19. On 22 July, China additionally announced that it plans to provide a US$1 billion loan to make its vaccine accessible for countries in Latin America and the Caribbean. On August 24, Chinese Premier Li Keqiang announced it would provide five Southeast Asian countries of Cambodia, Laos, Myanmar, Thailand and Vietnam priority access to the vaccine once it was fully developed.
Among European Union countries, France announced a US$4.9 million investment in a COVID‑19 vaccine research consortium via CEPI 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. In March, the European Commission made an €80 million investment in CureVac, a German biotechnology company, to develop a mRNA vaccine. The German government announced a separate €300 million investment in CureVac in June. Belgium, Norway, Switzerland, Germany, and the Netherlands have been major contributors to the CEPI effort for COVID‑19 vaccine research in Europe.
In April, the UK government formed a COVID‑19 vaccine task force to stimulate British efforts for rapidly developing a vaccine through collaborations of industry, universities, and government agencies across the vaccine development pipeline, including clinical trial placement at UK hospitals, regulations for approval, and eventual manufacturing. The vaccine development initiatives at the University of Oxford and Imperial College of London were financed with GB£44 million in April.
The 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. On 16 April, BARDA made a US$483 million investment in the vaccine developer, Moderna and its partner, Johnson & Johnson. 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. On 15 May, the US government announced federal funding for a fast-track program called Operation Warp Speed, which has the goals of placing 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 chief advisor is Moncef Slaoui and its Chief Operating Officer is Army General Gustave Perna. In June, the Warp Speed team said it would work with seven companies developing COVID‑19 vaccine candidates: Moderna, Johnson & Johnson, Merck, Pfizer, and the University of Oxford in collaboration with AstraZeneca, as well as two others.
WHO COVID-19 trials
In April 2020, the WHO published an "R&D Blueprint (for the) novel Coronavirus" (Blueprint). The Blueprint 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 Blueprint listed 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. 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; 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 – 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. 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.
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. 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. 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.
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.
Partnerships, competition, and distribution
Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), are forming alliances with biotechnology companies, national governments, and universities to accelerate progression to an effective vaccine. To combine financial and manufacturing capabilities for a pandemic adjuvanted vaccine technology, GSK joined with Sanofi in an uncommon partnership of multinational companies to support accelerated vaccine development.
During a pandemic on the rapid timeline and scale of COVID‑19 infections during 2020, international organizations like the WHO and CEPI, vaccine developers, governments, and industry are evaluating distribution of the eventual vaccine(s). Individual countries producing a vaccine may be persuaded to favor the highest bidder for manufacturing or provide first-service to their own country. Experts emphasize that licensed vaccines should be available and affordable for people at the frontline of healthcare and having the greatest need. 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 the WHO. Several companies plan to initially manufacture a vaccine at low cost, then increase costs for profitability later if annual vaccinations are needed and as countries build stock for future needs.
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. 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. The WHO, CEPI, and GAVI have expressed concerns that affluent countries should not receive priority access to the global supply of eventual COVID‑19 vaccines, but rather protecting healthcare personnel and people at high risk of infection are needed to address public health concerns and reduce economic impact of the pandemic.
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. 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.
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, 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". 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. From Phase I clinical trials, 84–90%of vaccine candidates fail to make it to final approval during development, and from Phase III, 25.7% fail – the investment by a manufacturer in a vaccine candidate may exceed US$1 billion and end with millions of useless doses. 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; an efficacy of less than 60% will not provide enough herd immunity to stop the spread of the virus alone.
As the pandemic expands during 2020, research at universities is obstructed by physical distancing and closing of laboratories. Globally, supplies critical to vaccine research and development are increasingly scarce due to international competition or national sequestration. 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.
CEPI scientists reported in September 2020 that nine different technology platforms – with the technology of numerous candidates remaining undefined – were under research and development during 2020 to create an effective vaccine against COVID‑19. According to CEPI, most of the platforms of vaccine candidates in clinical trials as of September are focused on the coronavirus spike protein and its variants as the primary antigen of COVID-19 infection. Platforms being developed in 2020 involve nucleic acid technologies (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 precision on COVID‑19 infection mechanisms. Vaccine platforms in development may improve flexibility for antigen manipulation and effectiveness for targeting mechanisms of COVID‑19 infection in susceptible population subgroups, such as healthcare workers, the elderly, children, pregnant women, and people with existing weakened immune systems.
|Molecular platform ^||Total number
|Number of candidates |
in human trials
|Non-replicating viral vector|
|Replicating viral vector|
|Live attenuated virus|
- One or more candidates in Phase II or Phase II–III trials
^ technologies for dozens of candidates are unannounced or "unknown"
CEPI classifies development stages for vaccines as "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. Some 321 total vaccine candidates are in development as either confirmed projects in clinical trials or in early-stage "exploratory" or "preclinical" development, as of September.
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.
Clinical trials started in 2020
|Technology||Current phase (participants)
|Completed phase[a] (participants)
Immune response, adverse effects
|Clinical trial site(s)||Duration[b]|
University of Oxford, AstraZeneca
|Modified chimp adenovirus vector (ChAdOx1)||Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity. Brazil (5,000) International enrolment of the Phase III trial was paused on 8 September 2020 due to an adverse neurological event in one participant, but resumed on 12 September after it was determined the symptoms were unrelated to the vaccine.
|Phase I-II (543)
Spike-specific antibodies at day 28; neutralizing antibodies after a booster dose at day 56. Adverse effects: pain at the injection site, headache, fever, chills, muscle ache, malaise in more than 60% of participants; paracetamol allowed for some participants to increase tolerability
|20 in the UK, São Paulo||May 2020 – Aug 2021|
Sinopharm: Beijing Institute of Biological Products, Wuhan Institute of Biological Products
|Inactivated SARS-CoV-2 (vero cells)||Phase III (48,000)
Randomized, double-blind, parallel placebo-controlled, to evaluate safety and protective efficacy in the United Arab Emirates, Bahrain, Jordan, and Argentina
On September 14, UAE approved Sinopharm's vaccine for emergency use by front-line healthcare workers following successful interim results in the Phase III trials.
|Phase I-II (320)
Neutralizing antibodies at day 14 after 2 injections; Adverse effects: injection site pain and fever, which were mild and self-limiting; no serious effects
|Jiaozuo, Abu Dhabi||Jul 2020 – Jul 2021 in Abu Dhabi|
CanSinoBIO, Beijing Institute of Biotechnology of the Academy of Military Medical Sciences[d]
|Recombinant adenovirus type 5 vector||Phase III (40,000)
global multi-center, randomized, double-blind, placebo-controlled to evaluate efficacy, safety and immunogenicity
|Phase II (508)
Neutralizing antibody and T cell responses. Adverse effects: moderate over 7 days: 74% had fever, pain, fatigue
|Wuhan, China||Mar – Dec 2020 in China
Sep 2020 – December 2021 in Pakistan
|Inactivated SARS-CoV-2||Phase III (10,490)
Double-blind, randomized, placebo-controlled to evaluate efficacy and safety in Brazil (8,870); Indonesia (1,620)
|Phase II (600)
Preprint. Immunogenicity eliciting 92% seroconversion at lower dose; Adverse effects: mild in severity, pain at injection site
|2 in China; 12 in Brazil; Bandung, Indonesia|
|BNT162 a1, b1, b2, c2
BioNTech, Fosun Pharma, Pfizer
|mRNA||Phase III (30,000)
|Phase I-II (60)
Preprint. Strong RBD-binding IgG and neutralizing antibody response peaked 7 days after a booster dose, robust CD4+ and CD8+ T cell responses, undetermined durability. Adverse effects: dose-dependent and moderate including pain at the injection site, fatigue, headache, chills, muscle and join pain, fever
|62 in the US, Germany||Apr 2020 – May 2021|
Moderna, NIAID, BARDA
|Lipid nanoparticle dispersion containing mRNA||Phase III (30,000)
Interventional; randomized, placebo-controlled study for efficacy, safety, and immunogenicity
|Phase I (45)
Dose-dependent neutralizing antibody response on two-dose schedule; undetermined durability. Adverse effects: fever, fatigue, headache, muscle ache, and pain at the injection site
|89 in the US||Jul 2020 – Oct 2022|
Gamaleya Research Institute of Epidemiology and Microbiology; trade name: Sputnik V
|Non-replicating viral vector||Phase III (40,000)
Randomized double-blind, placebo-controlled to evaluate efficacy, immunogenicity, and safety
|Phase I-II (76)
||Moscow||Aug 2020 – May 2021|
|Ad26.COV2.S||Non-replicating viral vector||Phase III (60,000)
Randomized, double-blinded, placebo-controlled
Temporarily paused on October 13 2020 due to an unexplained illness in a participant.
|Phase I-II (1,045)
||291 in US, Argentina, Brazil, Chile, Colombia, Mexico, Peru, Philippines, South Africa and Ukraine||Jul 2020 – 2023|
Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.
|Recombinant protein subunit||Phase II (900)
Interventional; randomized, double-blind, placebo-controlled 
|Phase I (50)
||Chongqing||Jun 2020 – Sep 2021|
|mRNA||Phase II (691)
Partially observer-blind, multicenter, controlled, dose-confirmation
|Phase I (168)
||Ghent, 3 in Germany||Jun 2020 – Aug 2021|
|SARS-CoV-2 recombinant spike protein nanoparticle with adjuvant||Phase II (131)
||Phase I (131)
Preprint. IgG and neutralizing antibody response with adjuvant after booster dose. Adverse effects: short-duration, low grade, local pain, headache, fatigue, myalgia
|2 in Australia||May 2020 – Jul 2021|
Inovio, CEPI, Korea National Institute of Health, International Vaccine Institute
|DNA plasmid delivered by electroporation||Phase I-II (40)
||Pending Phase I report||3 in the US, Seoul||Apr–Nov 2020|
Chinese Academy of Medical Sciences
|Inactivated SARS-CoV-2||Phase I-II (942)
Randomized, double-blinded, single-center, placebo-controlled
|Chengdu||Jun 2020 – Sep 2021|
AnGes Inc., AMED
|DNA plasmid||Phase I-II (30)
Non-randomized, single-center, two doses
|Osaka||Jun 2020 – Jul 2021|
|Lunar-COV19/ARCT-021||mRNA||Phase I-II (92)
|Singapore||Aug 2020 – ?|
Shenzhen Genoimmune Medical Institute
|Lentiviral vector with minigene modifying aAPCs||Phase I (100)
||Shenzhen||Mar 2020 – 2023|
Shenzhen Genoimmune Medical Institute
|Lentiviral vector with minigene modifying DCs||Phase I (100)
||Shenzhen||Mar 2020 – 2023|
MRC clinical trials unit at Imperial College London
|mRNA||Phase I (105)
Randomized trial, with dose escalation study (15) and expanded safety study (at least 200)
|4 in the UK||Jun 2020 – Jul 2021|
Genexine consortium, International Vaccine Institute
|DNA||Phase I (40)
||Seoul||Jun 2020 – Jun 2022|
Clover Biopharmaceuticals, GSK
|Spike protein trimeric subunit with GSK adjuvant||Phase I (150)
||Perth||Jun 2020 – Mar 2021|
Vaxine Pty Ltd
|Recombinant protein||Phase I (40)
||Adelaide||Jun 2020 – Jul 2021|
PLA Academy of Military Science, Walvax Biotech
|mRNA||Phase I (168)
||2 in China||Jun 2020 – Dec 2021|
Medicago (governments of Canada and Quebec)
|Recombinant plant-based VLP[g] with GSK adjuvant||Phase I (180)
|2 in Canada||Jul 2020 – Apr 2021|
UQ, Syneos Health, CEPI, Seqirus
|Molecular clamp stabilized spike protein with MF59||Phase I (120)
Randomised, double-blind, placebo-controlled, dose-ranging
- Latest Phase with published results.
- The range from the actual start date of Phase I to the estimated primary completion date of Phase III, when available.
- Oxford name: ChAdOx1 nCoV-19. Manufacturing in Brazil to be carried out by Oswaldo Cruz Foundation.
- Manufacturing partnership with the National Research Council of Canada and Canadian Center for Vaccinology, Halifax, Nova Scotia
- Four vaccines
- South Korean Phase I–II in parallel with Phase I in the US
- Virus-like particles grown in Nicotiana benthamiana
In April 2020, the WHO issued a statement representing dozens of vaccine scientists around the world, pledging collaboration to speed development of a vaccine against COVID‑19. 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.
Industry analysis of past vaccine development shows failure rates of 84–90%. 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.
To assess potential for vaccine efficacy, unprecedented computer simulations and new COVID‑19-specific animal models are being developed multinationally during 2020, but these methods remain untested by unknown characteristics of the COVID‑19 virus. 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.
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.
Scheduled Phase I trials in 2020
Many vaccine candidates under design or preclinical development for COVID‑19 will not gain approval for human studies in 2020 due to toxicity, ineffectiveness to induce immune responses or dosing failures in laboratory animals, or because of underfunding. The probability of success for an infectious disease vaccine candidate to pass preclinical barriers and reach Phase I of human testing is 41-57%.
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. 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.
Assertions have been made that COVID‑19 mortality has been lower in countries having routine BCG vaccine administered against tuberculosis, though the World Health Organization (WHO) has said there is no evidence that this vaccine is effective against the COVID‑19 virus. 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. A further randomized trial in Australia is seeking to enroll 4,170 healthcare workers.
Use of adjuvants
In September 2020, eleven of the vaccine candidates in clinical development used 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. A potential drawback of adjuvanted vaccines is that the virus evolves in a way to avoid the induced vaccine response, making the adjuvant-vaccine technology misdesigned against a changed virus. Such a change would require revised manufacturing and increased costs that discourage the routine use of adjuvants.
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. 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, and CEPI indicates a potential success rate of only 10% for vaccine candidates in 2020 development.
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." However, some 10% of the public perceives vaccines as unsafe or unnecessary, refusing vaccination – a global health threat called vaccine hesitancy – which increases the risk of further viral spread that could lead to COVID‑19 outbreaks. In mid-2020, estimates from two surveys were that 67% or 80% of people in the U.S. would accept a new vaccination against COVID-19, with wide disparity by education level, employment status, race, and geography.
Early research to assess vaccine efficacy using COVID‑19-specific animal models, such as ACE2-transgenic mice, other laboratory animals, and non-human primates, indicates a need for biosafety-level 3 containment measures for handling live viruses, and international coordination to ensure standardized safety procedures.
Although the quality and quantity of antibody production by a potential vaccine is intended to neutralize the COVID‑19 infection, a vaccine may have an unintended opposite effect by causing antibody-dependent disease enhancement (ADE), which increases the virus attachment to its target cells and might trigger the cytokine storm when the person will be infected by the virus after vaccination. The vaccine technology platform (for example, viral vector vaccine, spike (S) protein vaccine or protein subunit vaccine), 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. 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).
The effectiveness of new vaccine is defined by its efficacy. The efficacy of less than 60% may result in failure to create herd immunity. Host-("vaccinee")-related determinants that render a person susceptible to infection, such as genetics, health status (underlying disease, nutrition, pregnancy, sensitivities or allergies), immune competence, age, and economic impact or cultural environment can be primary or secondary factors affecting the severity of infection and response to a vaccine. Elderly (above age 60), allergen-hypersensitive, and obese people have susceptibility to compromised immunogenicity, which prevents or inhibits vaccine effectiveness, possibly requiring separate vaccine technologies for these specific populations or repetitive booster vaccinations to limit virus transmission. Further, mutations of the virus can alter its structure targeted by the vaccine, thus making the vaccine ineffective.
Enrollment of participants in trials
Vaccine developers have to invest resources internationally to find enough participants for Phase II–III clinical trials when the virus has proved to be a "moving target" of changing transmission rate across and within countries, forcing companies to compete for trial participants. As an example in June, the Chinese vaccine developer Sinovac formed alliances in Malaysia, Canada, the UK, and Brazil among its plans to recruit trial participants and manufacture enough vaccine doses for a possible Phase III study in Brazil where COVID‑19 transmission was accelerating during June. As the COVID‑19 pandemic within China became more isolated and controlled, Chinese vaccine developers sought international relationships to conduct advanced human studies in several countries, creating competition for trial participants with other manufacturers and the international Solidarity trial organized by the WHO. In addition to competition over recruiting participants, clinical trial organizers may encounter people unwilling to be vaccinated due to vaccine hesitancy or disbelieving the science of the vaccine technology and its ability to prevent infection.
Having an insufficient number of skilled team members to administer vaccinations may hinder clinical trials that must overcome risks for trial failure, such as recruiting participants in rural or low-density geographic regions, and variations of age, race, ethnicity, or underlying medical conditions.
An effective vaccine for COVID-19 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. It is not yet known if it is possible to create a safe, reliable and affordable vaccine for this virus, and it is not yet known exactly how much the vaccine development will cost. It is possible that billions of dollars could be invested without success.
The European Commission organized and held a video conference of world leaders on 4 May 2020, at which US$8 billion was raised for COVID-19 vaccine development.
After a vaccine is created, 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.
Different vaccines have different shipping and handling requirements. For example, the Pfizer/BioNTech vaccine BNT162 must be shipped and stored at −70 °C (−94 °F), must be used within five days of thawing, and has a minimum order of 975 doses, making it unlikely to be rolled out in settings other than large, well-equipped hospitals.
Proposed challenge studies
Strategies are being considered for fast-tracking the licensing of a vaccine against COVID‑19, especially by compressing (to a few months) the usually lengthy duration of Phase II–III trials (typically many years). Challenge studies have been implemented previously for diseases less deadly than COVID‑19 infection, such as common influenza, typhoid fever, cholera, and malaria. Following preliminary proof of safety and efficacy of a candidate vaccine in laboratory animals and healthy humans, controlled challenge studies might be implemented to bypass typical Phase III research, providing an accelerated path to license a COVID‑19 vaccine.
A challenge study begins by simultaneously testing a vaccine candidate for immunogenicity and safety in laboratory animals and healthy adult volunteers (100 or fewer), something normally a sequential process using animals first. If the initial tests are promising, the study proceeds by rapidly advancing the 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. Following the challenge, the volunteers would be monitored closely in clinics with life-saving resources, if needed. 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.
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 to rapidly produce an effective vaccine that will minimize the projected millions of deaths worldwide from COVID‑19 infection, according to some infectious disease experts. The World Health Organization has developed a guidance document with criteria for conducting COVID‑19 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.
A vaccine licensure occurs after the successful conclusion of the clinical trials program through Phases I–III demonstrating safety, immunogenicity at a specific dose, effectiveness at preventing infection in target populations, and enduring preventive effect. As part of a multinational licensure for a vaccine, the World Health Organization Expert Committee on Biological Standardization developed guidelines of international standards for manufacturing and quality control of vaccines, a process intended as a platform for national regulatory agencies to apply for their own licensure process. Vaccine manufacturers do not receive licensure until a complete clinical package proves the vaccine is safe and has long-term effectiveness, following scientific review by a multinational or national regulatory organization, such as the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA).
Upon developing countries adopting WHO guidelines for vaccine development and licensure, each country has its own responsibility to issue a national licensure, and to manage, deploy, and monitor the vaccine throughout its use in each nation. Building trust and acceptance of a licensed vaccine among the public is a task of communication by governments and healthcare personnel to ensure a vaccination campaign proceeds smoothly, saves lives, and enables economic recovery. When a vaccine is licensed, it will initially be in limited supply due to variable manufacturing, distribution, and logistical factors, requiring an allocation plan for the limited supply and which population segments should be prioritized to first receive the vaccine.
World Health Organization
Vaccines developed for multinational distribution via the United Nations Children's Fund (UNICEF) require pre-qualification by WHO to ensure international standards of quality, safety, immunogenicity, and efficacy for adoption by numerous countries.
The process requires manufacturing consistency at WHO-contracted laboratories following GMP practices. When UN agencies are involved in vaccine licensure, individual nations collaborate by 1) issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and 2) conducting postmarketing surveillance, including records for adverse events after the vaccination program. WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight.
Some countries choose to buy vaccines licensed by reputable national organizations, such as EMA, FDA, or national agencies in other affluent countries, but such purchases typically are more expensive and may not have distribution resources suitable to local conditions in developing countries.
In the European Union (EU), vaccines for pandemic pathogens, such as seasonal influenza, are licensed EU-wide where all of the member states comply ("centralized"), are licensed for only some member states ("decentralized"), or are licensed on an individual national level. Generally, all EU states follow regulatory guidance and clinical programs defined by the European Committee for Medicinal Products for Human Use (CHMP), a scientific panel of the European Medicines Agency (EMA) responsible for vaccine licensure. The CHMP is supported by several expert groups who assess and monitor the progress of a vaccine before and after licensure and distribution.
Under the FDA, the process of establishing evidence for vaccine clinical safety and efficacy is the same as for the approval process for prescription drugs. If successful through the stages of clinical development, the vaccine licensing process is followed by a Biologics License Application which must provide a scientific review team (from diverse disciplines, such as physicians, statisticians, microbiologists, chemists) a comprehensive documentation for the vaccine candidate having efficacy and safety throughout its development. Also during this stage, the proposed manufacturing facility is examined by expert reviewers for GMP compliance, and the label must have compliant description to enable health care providers definition of vaccine specific use, including its possible risks, to communicate and deliver the vaccine to the public.
As of August 2020 in the United States, there is no national strategy for how a successful vaccine will be ethically prioritized or distributed to vulnerable population segments, such as homeless and incarcerated people and the elderly. After licensure, monitoring of the vaccine and its production, including periodic inspections for GMP compliance, continue as long as the manufacturer retains its license, which may include additional submissions to the FDA of tests for potency, safety, and purity for each vaccine manufacturing step.
At the beginning of the COVID-19 pandemic in early 2020, the WHO issued a guideline as an Emergency Use Listing of new vaccines, a process derived from the 2013-16 Ebola epidemic. It required that a vaccine candidate developed for a life-threatening emergency be manufactured using GMP and that it complete development according to WHO prequalification procedures.
Even as new vaccines are developed during the COVID-19 pandemic, licensure of COVID-19 vaccine candidates requires submission of a full dossier of information on development and manufacturing quality. In the EU, companies may use a rolling review process, supplying data as they become available during Phase III trials, rather than developing the full documentation over months or years at the end of clinical research, as is typical. This rolling process allows the European CHMP to evaluate clinical data in real time, enabling a promising vaccine candidate to be approved on a rapid timeline by the EMA.
On June 24, 2020, China approved the CanSino vaccine for limited use in the military and two inactivated virus vaccines for emergency use in high-risk occupations. On August 11, 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.
In the United States, the FDA may grant Emergency Use Authorization for a promising COVID-19 vaccine before full evidence is available about its safety and efficacy, but this hastened process has been criticized for its political misuse, potential for lowered standards, and increased antivaccine sentiment in the US population during 2020. On September 8, 2020, nine leading pharma companies involved in COVID-19 vaccine research signed a letter, pledging that they would submit their vaccines for emergency use authorization only after phase 3 trials had demonstrated safety and efficacy.
Until a vaccine is in use for the general population, all potential adverse events from the vaccine may not be known, requiring manufacturers to conduct Phase IV studies for postmarketing surveillance of the vaccine while it is used widely in the public. The WHO works with UN member states to implement postlicensing surveillance. The FDA relies on a Vaccine Adverse Event Reporting System to monitor safety concerns about a vaccine throughout its use in the American public.
Commercialization and equitable access
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. The corporate investment and need to generate value for public shareholders raised concerns about a "market-based approach" in vaccine development, costly pricing of eventual licensed vaccines, preferred access for distribution first to affluent countries, and sparse or no distribution to where the pandemic is most aggressive, as predicted for densely-populated, impoverished countries unable to afford vaccinations. The collaboration of the University of Oxford with AstraZeneca (a global pharmaceutical company based in the UK) raised concerns about price and sharing of eventual profits from international vaccine sales, arising from whether the UK government and university as public partners had commercialization rights. AstraZeneca stated that initial pricing of its vaccine would not include a profit margin for the company while the pandemic was still expanding.
In early June, AstraZeneca made a USD$750 millon deal allowing CEPI and GAVI to manufacture and distribute 300 million doses if its Oxford vaccine candidate proves safe and effective, reportedly increasing the company's total production capacity to over 2 billion doses per year. Commercialization of pandemic vaccines is a high-risk business venture, potentially losing billions of dollars in development and pre-market manufacturing costs if the candidate vaccines fail to be safe and effective. The multinational pharmaceutical company Pfizer indicated it was not interested in a government partnership, which would be a "third party" slowing progress in Pfizer's vaccine program. Further, there are concerns that rapid-development programs – like the Operation Warp Speed plan of the United States – are choosing vaccine candidates mainly for their manufacturing advantages to shorten the development timeline, rather than for the most promising vaccine technology having safety and efficacy.
Favored distribution of vaccines within one or a few select countries, called "vaccine sovereignty", is a criticism of some of the vaccine development partnerships, such as for the AstraZeneca-University of Oxford vaccine candidate, concerning whether there may be prioritized distribution first within the UK and to the "highest bidder" – the United States, which made an advance payment of US$1.2 billion to secure 300 million vaccine doses for Americans, even before the AstraZeneca-Oxford vaccine or a Sanofi vaccine is proved safe or effective. Concerns exist about whether some countries producing vaccines may impose protectionist controls by export restrictions that would stockpile a COVID‑19 vaccine for their own population.
In June, the Serum Institute of India (SII) – a major manufacturer of global vaccines – reached a licensing agreement with AstraZeneca to make 1 billion doses of vaccine for low-and-middle income countries; of which half of the doses would go to India. Similar preferential homeland distribution may exist if a vaccine is manufactured in Australia. The Chinese government pledged in May that a successful Chinese vaccine would become a "global, public good," implying enough doses would be manufactured for both national and global distribution.
As many of the efforts on vaccine candidates have open-ended outcomes, including a high potential for failure during human testing, CEPI, WHO, and charitable vaccine organizations, such as the Gates Foundation and GAVI, raised over US$20 billion during the first half of 2020 to fund vaccine development and preparedness for vaccinations, particularly for children in under-developed countries. CEPI had stated that governments should ensure implementation of a globally-fair allocation system for eventual vaccines, using a coordinated system of manufacturing capacity, financing and purchasing, and indemnification from liability to offset risks taken by vaccine developers.
Having been created to monitor fair distribution of infectious disease vaccines to low- and middle-income countries, CEPI revised its equitable access policy that was published in February to apply to its COVID-19 vaccine funding: 1) "prices for vaccines will be set as low as possible for territories that are or may be affected by an outbreak of a disease for which CEPI funding was used to develop a vaccine;" 2) "information, know-how and materials related to vaccine development must be shared with (or transferred to) CEPI" so that it can assume responsibility for vaccine development if a company discontinues expenditures for a promising vaccine candidate; 3) CEPI would have access to, and possible management of, intellectual property rights (i.e., patents) for promising vaccines; 4) "CEPI would receive a share of financial benefits that might accrue from CEPI-sponsored vaccine development, to re-invest in support of its mission to provide global public health benefit"; and 5) data transparency among development partners should maintain the WHO Statement on Public Disclosure of Clinical Trial Results, and require results to be published in open-access publications. Some vaccine manufacturers opposed parts of these proposals.
International groups, such as the Centre for Artistic Activism and Universities Allied for Essential Medicines, advocate for equitable access to licensed COVID‑19 vaccines. Scientists have encouraged that the WHO, CEPI, corporations, and governments collaborate to assure evidence-based allocation of eventual COVID‑19 vaccines determined on infection risk, particularly urgent vaccinations provided first for healthcare workers, vulnerable populations, and children. During 2020, the WHO, GAVI, and CEPI combined resources to form COVAX – a program for coordination of global equitable access to a licensed vaccine.
Over 100 international scientists and concerned individuals (including those associated with religious organizations) have called for releasing COVID‑19 vaccines to the public domain. Similar to the development of the first polio vaccine that was never patented, an effective COVID-19 vaccine would be available for production and approval by a number of countries and pharmaceutical manufacturing centers worldwide, therefore allowing for a more even and cost-effective distribution on a global scale.
During and after 2021, deploying a COVID-19 vaccine may require worldwide transport and tracking of 10-19 billion vial doses, an effort readily becoming the largest supply chain challenge in history. As of September 2020, supply chain and logistics experts expressed concern that international and national networks for distributing a licensed vaccine were not ready for the volume and urgency, due mainly to deterioration of resources during 2020 pandemic lockdowns and downsizing that degraded supply capabilities. Addressing the worldwide challenge faced by coordinating numerous organizations – the COVAX partnership, global pharmaceutical companies, contract vaccine manufacturers, inter- and intranational transport, storage facilities, and health organizations in individual countries – Seth Berkley, chief executive of GAVI, stated: "Delivering billions of doses of vaccine to the entire world efficiently will involve hugely complex logistical and programmatic obstacles all the way along the supply chain."
As an example highlighting the immensity of the challenge, the International Air Transport Association stated that 8,000 747 cargo planes – implemented with equipment for precision vaccine cold storage – would be needed to transport just one dose for people in the more than 200 countries experiencing the COVID-19 pandemic. GAVI states that "with a fast-moving pandemic, no one is safe, unless everyone is safe."
In contrast to the multibillion dollar investment in vaccine technologies and early-stage clinical research, the post-licensing supply chain for a vaccine has not received the same planning, coordination, security or investment. A major concern is that resources for vaccine distribution in low- to middle-income countries, particularly for vaccinating children, are inadequate or non-existent, but could be improved with cost efficiencies if procurement and distribution were centralized regionally or nationally. In September, the COVAX partnership included 172 countries coordinating plans to optimize the supply chain for a COVID-19 vaccine, and the United Nations Children's Fund joined with COVAX to prepare the financing and supply chain for vaccinations of children in 92 developing countries.
Logistics vaccination services assure necessary equipment, staff, and supply of licensed vaccines across international borders. Central logistics include vaccine handling and monitoring, cold chain management, and safety of distribution within the vaccination network. The purpose of the COVAX Facility is to centralize and equitably administer logistics resources among participating countries, merging manufacturing, transport, and overall supply chain infrastructure. Included are logistics tools for vaccine forecasting and needs estimation, in-country vaccine management, potential for wastage, and stock management.
- visibility and traceability by barcodes for each vaccine vial
- sharing of supplier audits
- sharing of chain of custody for a vaccine vial from manufacturer to the individual being vaccinated
- use of vaccine temperature monitoring tools
- temperature stability testing and assurance
- new packaging and delivery technologies
- coordination of supplies within each country (personal protective equipment, diluent, syringes, needles, rubber stoppers, refrigeration fuel or power sources, waste-handling, among others)
- communications technology
- environmental impacts in each country
A logistics shortage in any one step may derail the whole supply chain, according to one vaccine developer. If the vaccine supply chain fails, the economic and human costs of the pandemic may be extended for years.
By August 2020 when only a few vaccine candidates were in Phase III trials many months from establishing safety and efficacy, numerous governments pre-ordered more than two billion doses at a cost of more than US$5 billion. Pre-orders from the UK government for 2021 were for five vaccine doses per person, a number dispiriting organizations like the WHO and GAVI which are promoting fair and equitable access worldwide, especially for developing countries. In September, CEPI was financially supporting basic and clinical research for nine vaccine candidates, with nine more in evaluation, under financing commitments to manufacture two billion doses of three licensed vaccines by the end of 2021. Overall before 2022, 7-10 billion COVID-19 vaccine doses may be manufactured worldwide, but the sizable pre-orders by affluent countries – called "vaccine nationalism" – threaten vaccine availability for poorer nations. Brazil and Indonesia had pre-ordered millions of vaccine doses that are undergoing phase III trials in their countries The Serum Institute of India plans to produce at least one billion vaccine doses, although the Institute has stated that half the doses will be used in India. After joining COVAX in October, China shared that it would produce 600 million vaccine doses before the end of 2020 and another one billion doses in 2021, although it was unsure how many would be for the country's own population of 1.4 billion.
AstraZeneca CEO, Pascal Soriot, stated: "The challenge is not making the vaccine itself, it's filling vials. There just aren't enough vials in the world." Preparing for high demand in manufacturing vials, an American glass producer invested $163 million in July for a vial factory. Glass availability for vial manufacturing and contaminant control are issues of concern, indicating higher production costs with lower profit potential for developers amid demands for vaccines to be affordable.
Vaccines must be handled and transported using international regulations, be maintained at controlled temperatures that vary across vaccine technologies, and be used for immunization before deterioration in storage. The scale of the COVID-19 vaccine supply chain is expected to be vast to ensure delivery worldwide to vulnerable populations. Priorities for preparing facilities for such distribution include temperature-controlled facilities and equipment, optimizing infrastructure, training immunization staff, and rigorous monitoring. RFID technologies are being implemented to track and authenticate a vaccine dose from the manufacturer along the entire supply chain to the vaccination.
Vaccines (and adjuvants) are inherently unstable during temperature changes, requiring cold chain management throughout the entire supply chain, typically at temperatures of 2–8 °C (36–46 °F). Because COVID-19 vaccine technologies are varied among several novel technologies, there are new challenges for cold chain management, with some vaccines that are stable while frozen but labile to heat, while others should not be frozen at all, and some are stable across temperatures. Freezing damage and inadequate training of personnel in the local vaccination process are major concerns. If more than one COVID-19 vaccine is approved, the vaccine cold chain may have to accommodate all these temperature sensitivities across different countries with variable climate conditions and local resources for temperature maintenance.
DNA and RNA vaccine technologies are in development, but may be difficult to manufacture at scale and control degradation during cold storage and transport. As examples, Moderna's RNA vaccine candidate requires cold chain management just above freezing temperatures with limited storage duration, but the BioNTech-Pfizer RNA candidate requires storage at -70°C (-94°F) or colder throughout deployment until vaccination.
After a vaccine vial is punctured to administer a dose, it is viable for only six hours, then must be discarded, requiring attention to local management of cold storage and vaccination processes. Because the COVID-19 vaccine will likely be in short supply for many locations during early deployment, vaccination staff will have to avoid spoilage and waste, which typically are as much as 30% of the supply. The cold chain is further challenged by the type of local transportation for the vaccines in rural communities, such as by motorcycle or delivery drone, need for booster doses, use of diluents, and access to vulnerable populations, such as healthcare staff, children and the elderly.
Air and land transport
Coordination of international air cargo is an essential component of time- and temperature-sensitive distribution of COVID-19 vaccines, but, as of September 2020, the air freight network is not prepared for multinational deployment. "Safely delivering COVID-19 vaccines will be the mission of the century for the global air cargo industry. But it won't happen without careful advance planning. And the time for that is now. We urge governments to take the lead in facilitating cooperation across the logistics chain so that the facilities, security arrangements and border processes are ready for the mammoth and complex task ahead," said IATA's Director General and CEO, Alexandre de Juniac, in September 2020.
For the severe reduction in passenger air traffic during 2020, airlines downsized personnel, trimmed destination networks, and put aircraft into long-term storage. As the lead agencies for procurement and supply of the COVID-19 vaccine within the WHO COVAX Facility, GAVI and UNICEF are preparing for the largest and fastest vaccine deployment ever, necessitating international air freight collaboration, customs and border control, and possibly as many as 8,000 cargo planes to deliver just one vaccine dose to multiple countries.
Security and corruption
Medicines are the world's largest fraud market, worth some $200 billion per year, making the widespread demand for a COVID-19 vaccine vulnerable to counterfeit, theft, scams, and cyberattacks throughout the supply chain. Anticorruption, transparency, and accountability safeguards are being established to reduce and eliminate corruption of COVID-19 vaccine supplies. Absence of harmonized regulatory frameworks among countries, including low technical capacity, constrained access, and ineffective capability to identify and track genuine vs. counterfeit vaccines, may be life-threatening for vaccine recipients, and would potentially perpetuate the COVID-19 pandemic. Tracking system technologies for packaging are being used by manufacturers to trace vaccine vials across the supply chain, and to use digital and biometric tools to assure security for vaccination teams.
The WHO has implemented an "Effective Vaccine Management" system, which includes constructing priorities to prepare national and subnational personnel and facilities for vaccine distribution, including:
- Trained staff to handle time- and temperature-sensitive vaccines
- Robust monitoring capabilities to ensure optimal vaccine storage and transport
- Temperature-controlled facilities and equipment
- Facilitating flight and landing permits
- Exempting flight crews from quarantine requirements
- Facilitating flexible operations for efficient national deployment
- Granting arrival priority to maintain vaccine temperature requirements
On February 4, 2020, US Secretary of Health and Human Services Alex Azar published a notice of declaration under the Public Readiness and Emergency Preparedness Act for medical countermeasures against COVID‑19, covering "any vaccine, used to treat, diagnose, cure, prevent, or mitigate COVID‑19, or the transmission of SARS-CoV-2 or a virus mutating therefrom", and stating that the declaration precludes "liability claims alleging negligence by a manufacturer in creating a vaccine, or negligence by a health care provider in prescribing the wrong dose, absent willful misconduct". The declaration is effective in the United States through 1 October 2024.
Social media posts have promoted a conspiracy theory that a COVID‑19 vaccine is already available. The patents cited by various social media posts have references to existing patents for genetic sequences and vaccines for other strains such as the SARS coronavirus, but not for COVID‑19.
On 21 May 2020, the FDA made public the cease-and-desist notice it had sent to North Coast Biologics, a Seattle-based company that had been selling a purported "nCoV19 spike protein vaccine".
- Diamond MS, Pierson TC (13 May 2020). "The challenges of vaccine development against a new virus during a pandemic". Cell Host and Microbe. 27 (5): 699–703. doi:10.1016/j.chom.2020.04.021. PMC 7219397. PMID 32407708.
- Le, Tung Thanh; Cramer, Jakob P.; Chen, Robert; Mayhew, Stephen (4 September 2020). "Evolution of the COVID-19 vaccine development landscape". Nature Reviews Drug Discovery. 19 (10): 667–68. doi:10.1038/d41573-020-00151-8. ISSN 1474-1776. PMID 32887942. S2CID 221503034.
- "COVID-19 vaccine development pipeline (Refresh URL to update)". Vaccine Centre, London School of Hygiene and Tropical Medicine. 14 September 2020. Retrieved 17 September 2020.
- "COVID-19 vaccine tracker (Choose vaccines tab, apply filters to view select data)". Milken Institute. 17 September 2020. Retrieved 16 September 2020. Lay summary.
- "Draft landscape of COVID 19 candidate vaccines". World Health Organization. 17 September 2020. Retrieved 17 September 2020.
- 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.
- "CEPI welcomes UK Government's funding and highlights need for $2 billion to develop a vaccine against COVID-19". Coalition for Epidemic Preparedness Innovations, Oslo, Norway. 6 March 2020. Archived from the original on 22 March 2020. Retrieved 23 March 2020.
- Wake D (4 May 2020). "EU spearheads $8 billion virus fundraiser". Yahoo Finance. Archived from the original on 29 June 2020. Retrieved 4 May 2020.
- "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization. 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- "SARS (severe acute respiratory syndrome)". National Health Service. 5 March 2020. Archived from the original on 9 March 2020. Retrieved 31 January 2020.
- Shehata MM, Gomaa MR, Ali MA, Kayali G (20 January 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.
- Butler D (October 2012). "SARS veterans tackle coronavirus". Nature. 490 (7418): 20. Bibcode:2012Natur.490...20B. doi:10.1038/490020a. PMID 23038444.
- 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.
- 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.
- "World Health Organization timeline – COVID-19". World Health Organization. 27 April 2020. Archived from the original on 29 April 2020. Retrieved 2 May 2020.
- Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, et al. (9 April 2020). "The COVID-19 vaccine development landscape". Nature Reviews Drug Discovery. 19 (5): 305–06. doi:10.1038/d41573-020-00073-5. ISSN 1474-1776. PMID 32273591. Archived from the original on 10 May 2020. Retrieved 11 April 2020.
- 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.
- 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.
- Grenfell R, Drew T (17 February 2020). "Here's Why It's Taking So Long to Develop a Vaccine for the New Coronavirus". ScienceAlert. Archived from the original on 28 February 2020. Retrieved 26 February 2020.
- 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.
- "Landmark global collaboration launched to defeat COVID-19 pandemic". CEPI. 24 April 2020. Archived from the original on 2 May 2020. Retrieved 2 May 2020.
The global nature of a pandemic means that any vaccine or medicine that is successfully developed will be needed immediately all over the world. That means that the challenge we face is not only one of R&D but one of manufacturing at scale, and equitable access.
- Schmidt, Charles (1 June 2020). "Genetic Engineering Could Make a COVID-19 Vaccine in Months Rather Than Years". Scientific American.
- Fox C, Kelion L (16 July 2020). "Russian spies 'target coronavirus vaccine'". BBC News Online. Retrieved 1 August 2020.
- "The Access to COVID-19 Tools (ACT) Accelerator". World Health Organization. 2020. Retrieved 29 August 2020.
- "COVAX: Ensuring global equitable access to COVID-19 vaccines". GAVI. 2020. Retrieved 28 August 2020.
- "More than 150 countries engaged in COVID-19 vaccine global access facility". World Health Organization. 15 July 2020. Retrieved 25 July 2020.
COVAX is the only truly global solution to the COVID-19 pandemic. For the vast majority of countries, whether they can afford to pay for their own doses or require assistance, it means receiving a guaranteed share of doses and avoiding being pushed to the back of the queue, as we saw during the H1N1 pandemic a decade ago. Even for those countries that are able to secure their own agreements with vaccine manufacturers, this mechanism represents, through its world-leading portfolio of vaccine candidates, a means of reducing the risks associated with individual candidates failing to show efficacy or gain licensure.
- 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.
- Sanger DE, Kirkpatrick DD, Zimmer C, Thomas K, Wee S (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.
- Hamilton IA (1 May 2020). "Bill Gates thinks there are 8 to 10 promising coronavirus vaccine candidates and one could be ready in as little as 9 months". Business Insider. Archived from the original on 16 May 2020. Retrieved 2 May 2020.
- "GloPID: Novel coronavirus COVID-19". glopid-r.org. Archived from the original on 2 May 2020. Retrieved 2 May 2020.
GloPID-R Members and other major players involved in infectious disease outbreaks worldwide reacted rapidly to this emerging epidemic, working closely with WHO to identify the specific funding research priorities needed to tackle the disease.
- "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.
- "ISARIC: COVID-19 clinical research resources". ISARIC. 27 April 2020. Archived from the original on 30 March 2020. Retrieved 2 May 2020.
- "Global Vaccine Summit 2020: World leaders make historic commitments to provide equal access to vaccines for all". Global Alliance for Vaccines and Immunisation. 4 June 2020. Archived from the original on 6 June 2020. Retrieved 4 June 2020.
- "Bill & Melinda Gates Foundation pledges US$1.6 billion to Gavi, the Vaccine Alliance, to protect the next generation with lifesaving vaccines" (Press release). The Bill & Melinda Gates Foundation. 4 June 2020. Archived from the original on 4 June 2020. Retrieved 4 June 2020 – via PR Newswire.
- 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.
- "Government of Canada funds 49 additional COVID-19 research projects – Details of the funded projects". Government of Canada. 23 March 2020. Archived from the original on 22 March 2020. Retrieved 23 March 2020.
- Aiello R (4 May 2020). "'A global challenge': PM Trudeau commits $850 million to global fight against COVID-19". CTV News. Archived from the original on 10 May 2020. Retrieved 4 May 2020.
- 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.
- Yuliya Talmazan, Keir Simmons, Laura Saravia (18 May 2020). "China's Xi announces $2B for coronavirus response as WHO faces calls for investigation". NBC News. Archived from the original on 18 May 2020. Retrieved 18 May 2020.CS1 maint: uses authors parameter (link)
- Ore, Diego (23 July 2020). "Mexico says China plans $1 billion loan to ease Latam access to virus vaccine". Reuters. Retrieved 16 August 2020.
- "China promises Mekong neighbours access to Chinese Covid-19 vaccine". South China Morning Post. 24 August 2020. Retrieved 24 August 2020.
- "CEPI: Our vaccine and platform portfolio". Coalition for Epidemic Preparedness Innovation (CEPI). 30 April 2020. Archived from the original on 7 May 2020. Retrieved 3 May 2020.
- "CEPI collaborates with the Institut Pasteur in a consortium to develop COVID-19 vaccine". Coalition for Epidemic Preparedness Innovations. 19 March 2020. Archived from the original on 22 March 2020. Retrieved 23 March 2020.
- "Coronavirus: Commission offers financing to innovative vaccines company CureVac". European Commission. 16 March 2020. Archived from the original on 19 March 2020. Retrieved 19 March 2020.
- "Corona-Impfstoff: Bundesregierung beteiligt sich an Impfstoffhersteller CureVac". www.spiegel.de (in German). Der Spiegel. Archived from the original on 16 June 2020. Retrieved 15 June 2020.
- Morriss E (22 April 2020). "Government launches coronavirus vaccine taskforce as human clinical trials start". Pharmafield. Retrieved 3 May 2020.
- Gartner A, Roberts L (3 May 2020). "How close are we to a coronavirus vaccine? Latest news on UK trials". The Telegraph. ISSN 0307-1235. Archived from the original on 4 May 2020. Retrieved 3 May 2020.
- "Landmark partnership announced for development of COVID-19 vaccine". University of Oxford. 30 April 2020. Archived from the original on 13 May 2020. Retrieved 3 May 2020.
- 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.
- Lee CE, Welker K, Perlmutter-Gumbiner E (1 May 2020). "Health officials eyeing at least one of 14 potential coronavirus vaccines to fast-track". NBC News. Archived from the original on 11 May 2020. Retrieved 2 May 2020.
- Cohen J (15 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. ISSN 0036-8075. PMID 32409451. Archived from the original on 19 May 2020. Retrieved 15 May 2020.
- Justin Sink, Jordan Fabian, Riley Griffin (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.CS1 maint: uses authors parameter (link)
- Riley Griffith, Jennifer Jacobs (3 June 2020). "White House Works With Seven Drugmakers in 'Warp Speed' Push". Bloomberg. Archived from the original on 3 June 2020. Retrieved 4 June 2020.CS1 maint: uses authors parameter (link)
- "An international randomised trial of candidate vaccines against COVID-19: Outline of Solidarity vaccine trial" (PDF). World Health Organization. 9 April 2020. Archived (PDF) from the original on 12 May 2020. Retrieved 9 May 2020.
- Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, et al. (February 2018). "Adaptive designs in clinical trials: why use them, and how to run and report them". BMC Medicine. 16 (1): 29. doi:10.1186/s12916-018-1017-7. PMC 5830330. PMID 29490655.
- "Adaptive designs for clinical trials of drugs and biologics: Guidance for industry". U.S. Food and Drug Administration (FDA). 1 November 2019. Archived from the original on 13 December 2019. Retrieved 3 April 2020.
- McGrail S (15 April 2020). "Sanofi, GSK partner to develop adjuvanted COVID-19 vaccine". PharmaNewsIntelligence. Archived from the original on 9 May 2020. Retrieved 4 May 2020.
- "R&D Blueprint: A coordinated global research roadmap – 2019 novel coronavirus" (PDF). World Health Organization. 1 March 2020. Archived (PDF) from the original on 15 May 2020. Retrieved 10 May 2020.
- 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.
- Wee S (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.
- 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. ISSN 1474-4457. PMC 7158580. PMID 32197097.
- "Clinical Development Success Rates 2006–2015" (PDF). BIO Industry Analysis. June 2016. Archived (PDF) from the original on 12 September 2019. Retrieved 23 March 2020.
- Blackwell T (20 April 2020). "COVID-19 vaccine researchers say pandemic lockdown placing many serious obstacles to their work". National Post. Retrieved 3 May 2020.
- 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.
- "Vaccine Safety – Vaccines". vaccines.gov. US Department of Health and Human Services. Archived from the original on 22 April 2020. Retrieved 13 April 2020.
- "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.
- Cohen J (19 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. Archived from the original on 21 June 2020. Retrieved 20 June 2020.
- "How flu vaccine effectiveness and efficacy are measured". Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, US Department of Health and Human Services. 29 January 2016. Retrieved 6 May 2020.
- "Principles of epidemiology, Section 8: Concepts of disease occurrence". Centers for Disease Control and Prevention, Center for Surveillance, Epidemiology, and Laboratory Services, US Department of Health and Human Services. 18 May 2012. Archived from the original on 6 April 2020. Retrieved 6 May 2020.
- Walsh N, Shelley J, Duwe E, Bonnett W (27 July 2020). "The world's hopes for a coronavirus vaccine may run in these health care workers' veins". CNN. São Paulo. Retrieved 3 August 2020.
- "Investigating a Vaccine Against COVID-19". ClinicalTrials.gov (Registry). United States National Library of Medicine. 26 May 2020. NCT04400838. Retrieved 14 July 2020.
- "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 (Registry). European Union. 21 April 2020. EudraCT 2020-001228-32. Retrieved 3 August 2020.
- O'Reilly P (26 May 2020). "A Phase III study to investigate a vaccine against COVID-19". ISRCTN (Registry). doi:10.1186/ISRCTN89951424. ISRCTN89951424. Retrieved 3 August 2020.
- "A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19". ClinicalTrials.gov (Registry). United States National Library of Medicine. 12 May 2020. NCT04383574. Retrieved 26 August 2020.
- "Trial of Oxford COVID-19 vaccine starts in Brazil". Jenner Institute. Retrieved 26 August 2020.
- Phillips, Nicky; Cyranoski, David; Mallapaty, Smriti (9 September 2020). "A leading coronavirus vaccine trial is on hold: scientists react". Nature. doi:10.1038/d41586-020-02594-w. ISSN 0028-0836. PMID 32908295. S2CID 221620587.
- Adam Feuerstein (9 September 2020). "Covid-19 vaccine trial participant had serious neurological symptoms, but could be discharged today, AstraZeneca CEO says". STAT. Retrieved 10 September 2020.
- "AstraZeneca en universiteit Oxford hervatten vaccintest". NOS (in Dutch). 12 September 2020. Retrieved 12 September 2020.
- Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. (July 2020). "Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial" (PDF). Lancet. 396 (10249): 467–78. doi:10.1016/S0140-6736(20)31604-4. PMC 7445431. PMID 32702298. Lay summary.
- Chen, Wei; Al Kaabi, Nawal (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.
- Yang, Yunkai. "A Study to Evaluate The Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above". clinicaltrials.gov. Clinical Trials. Retrieved 15 September 2020.
- "Clinical Trial to Evaluate the Efficacy, Immunogenicity and Safety of the Inactivated SARS-CoV-2 Vaccine (COVID-19)". clinicaltrials.gov. Retrieved 28 September 2020.
- Maxwell, Chris. "Coronavirus: UAE authorises emergency use of vaccine for frontline workers". The National. Retrieved 14 September 2020.
- Xia S, Duan K, Zhang Y, Zhao D, et al. (13 August 2020). "Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials". JAMA. doi:10.1001/jama.2020.15543. PMC 7426884. PMID 32789505.
- "The National Research Council of Canada and CanSino Biologics Inc. announce collaboration to advance vaccine against COVID-19". National Research Council, Government of Canada. 12 May 2020. Archived from the original on 22 May 2020. Retrieved 22 May 2020.
- Gou, Jinbo. "Phase III Trial of A COVID-19 Vaccine of Adenovirus Vector in Adults 18 Years Old and Above". clinicaltrials.gov. Retrieved 17 September 2020.
- Zhu F, Guan X, Li Y, Huang J, Jiang T, Hou L, et al. (July 2020). "Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial" (PDF). Lancet. 396 (10249): 479–88. doi:10.1016/s0140-6736(20)31605-6. ISSN 0140-6736. PMID 32702299. Lay summary.
- "Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of SARS-CoV-2 Infection (COVID-19) (Renqiu)". ClinicalTrials.gov (Registry). United States National Library of Medicine. 12 May 2020. NCT04383574. Retrieved 14 July 2020.
- "Clinical Trial of Efficacy and Safety of Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine in Healthcare Professionals (PROFISCOV)". ClinicalTrials.gov (Registry). United States National Library of Medicine. 2 July 2020. NCT04456595. Retrieved 3 August 2020.
- 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.
- Zhang Y-J, Zeng G, Pan H-X, Li C-G, others (10 August 2020). "Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18–59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial". MedRxiv. doi:10.1101/2020.07.31.20161216. S2CID 221089937.CS1 maint: uses authors parameter (link)
- Indonesia, C. N. N. "Fakta Terbaru Uji Klinis Vaksin Covid-19 di Bandung". teknologi (in Indonesian). Retrieved 26 August 2020.
- "Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Adults". ClinicalTrials.gov (Registry). United States National Library of Medicine. 30 April 2020. NCT04368728. Retrieved 14 July 2020.
- "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 (Registry). European Union. 14 April 2020. EudraCT 2020-001038-36. Archived from the original on 22 April 2020. Retrieved 22 April 2020.
- Lovelace Jr B (27 July 2020). "Pfizer and BioNTech began late-stage human trial for coronavirus vaccine Monday". CNBC. Retrieved 3 August 2020.
- Mulligan M, Lyke K, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. (1 July 2020). "Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report" (PDF). MedRxiv (Preprint). doi:10.1101/2020.06.30.20142570. S2CID 220266992. Retrieved 3 August 2020.
- Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, et al. (2020). "Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine" (PDF). MedRxiv (Preprint). doi:10.1101/2020.07.17.20140533. Lay summary.
- "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 (Registry). United States National Library of Medicine. 14 July 2020. NCT04470427. Retrieved 27 July 2020.
- Palca J (27 July 2020). "COVID-19 vaccine candidate heads to widespread testing in U.S." NPR. Retrieved 27 July 2020.
- Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. (mRNA-1273 Study Group) (July 2020). "An mRNA Vaccine against SARS-CoV-2 – Preliminary Report". New England Journal of Medicine. doi:10.1056/NEJMoa2022483. PMC 7377258. PMID 32663912. Lay summary.
- Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. (mRNA-1273 Study Group) (July 2020). "An mRNA Vaccine against SARS-CoV-2 – Preliminary Report Supplementary appendix" (PDF). New England Journal of Medicine. doi:10.1056/NEJMoa2022483. PMID 32663912.
- "Clinical Trial of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Vaccine Against COVID-19". clinicaltrials.gov.
- Logunov, Denis Y; Dolzhikova, Inna V; others (2020). "Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia". The Lancet. 396 (10255): 887–97. doi:10.1016/s0140-6736(20)31866-3. ISSN 0140-6736. PMID 32896291. S2CID 221472251.
- "A Study of Ad26.COV2.S in Adults". ClinicalTrials.gov, US National Library of Medicine. 4 August 2020. Retrieved 23 August 2020.
- Sadoff, Jerry; Le Gars, Mathieu; Shukarev, Georgi; Heerwegh, Dirk; Truyers, Carla; de Groot, Anna Marit; Stoop, Jeroen; Tete, Sarah; Van Damme, Wim; Leroux-Roels, Isabel; Berghmans, Pieter-Jan (25 September 2020). "Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate: interim results of a phase 1/2a, double-blind, randomized, placebo-controlled trial". doi:10.1101/2020.09.23.20199604. S2CID 221882008. Cite journal requires
- "A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants". ClinicalTrials.gov. US National Library of Medicine.
- "Johnson & Johnson Temporarily Pauses All Dosing in Our Janssen COVID-19 Vaccine Candidate Clinical Trials".
- "Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine". ClinicalTrials.gov (Registry). United States National Library of Medicine. 24 June 2020. NCT04445194. Retrieved 14 July 2020.
- "A Randomized, Blinded, Placebo-controlled Trial to Evaluate the Immunogenicity and Safety of a Recombinant New Coronavirus Vaccine (CHO Cell) With Different Doses and Different Immunization Procedures in Healthy People Aged 18 to 59 Years". ClinicalTrials.gov (Registry). United States National Library of Medicine. 10 July 2020. NCT04466085. Retrieved 26 August 2020.
- "A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults". ClinicalTrials.gov, US National Library of Medicine. 26 June 2020. NCT04449276. Retrieved 14 July 2020.
- "A Dose-Confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults". ClinicalTrials.gov, US National Library of Medicine. 17 August 2020. NCT04515147. Retrieved 28 August 2020.
- "Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrix-M Adjuvant". ClinicalTrials.gov (Registry). United States National Library of Medicine. 30 April 2020. NCT04368988. Retrieved 14 July 2020.
- "NVX-CoV2373 COVID-19 Vaccine Candidate Phase 1/2, Part 1, Clinical Trial Results" (PDF). 4 August 2020. Retrieved 5 August 2020. Lay summary.
- Keech, Cheryl; Albert, Gary; Reed, Patricia; Neal, Susan; Plested, Joyce; Zhu, Mingzhu; et al. (6 August 2020). "First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine" (PDF). MedRxiv (Preprint). doi:10.1101/2020.08.05.20168435. S2CID 221004959. Retrieved 7 August 2020.
- "Safety, Tolerability and Immunogenicity of INO-4800 for COVID-19 in Healthy Volunteers". ClinicalTrials.gov (Registry). United States National Library of Medicine. 7 April 2020. NCT04336410. Retrieved 14 July 2020.
- "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.
- "Safety and Immunogenicity Study of an Inactivated SARS-CoV-2 Vaccine for Preventing Against COVID-19". ClinicalTrials.gov (Registry). United States National Library of Medicine. 2 June 2020. NCT04412538. Retrieved 14 July 2020.
- "Study of COVID-19 DNA Vaccine (AG0301-COVID19)". ClinicalTrials.gov (Registry). United States National Library of Medicine. 9 July 2020. NCT04463472. Retrieved 14 July 2020.
- "About AnGes – Introduction". AnGes, Inc. Retrieved 1 August 2020.
- "CTI and Arcturus Therapeutics Announce Initiation of Dosing of COVID-19 STARR™ mRNA Vaccine Candidate, LUNAR-COV19 (ARCT-021) in a Phase 1/2 study". UK BioIndustry Association. 13 August 2020. Retrieved 23 August 2020.
- "Ascending Dose Study of Investigational SARS-CoV-2 Vaccine ARCT-021 in Healthy Adult Subjects". clinicaltrials.gov. Retrieved 23 August 2020.
- "Safety and Immunity of Covid-19 aAPC Vaccine". ClinicalTrials.gov (Registry). United States National Library of Medicine. 9 March 2020. NCT04299724. Retrieved 14 July 2020.
- "About Us". Shenzhen Genoimmune Medical Institute. Retrieved 1 August 2020.
- "Immunity and Safety of Covid-19 Synthetic Minigene Vaccine". ClinicalTrials.gov (Registry). United States National Library of Medicine. 19 February 2020. NCT04276896. Retrieved 14 July 2020.
- Ward D, McCormack S (22 May 2020). "Clinical trial to assess the safety of a coronavirus vaccine in healthy men and women". ISRCTN (Registry). doi:10.1186/ISRCTN17072692. ISRCTN17072692. Retrieved 8 June 2020.
- "Safety and Immunogenicity Study of GX-19, a COVID-19 Preventive DNA Vaccine in Healthy Adults". ClinicalTrials.gov (Registry). United States National Library of Medicine. 24 June 2020. NCT04445389. Retrieved 14 July 2020.
- "S. Korea's Genexine begins human trial of coronavirus vaccine". Reuters. 19 June 2020. Retrieved 25 June 2020.
- "Genexine consortium's Covid-19 vaccine acquires approval for clinical trails in Korea". 11 June 2020. Retrieved 1 August 2020.
- "SCB-2019 as COVID-19 Vaccine". ClinicalTrials.gov (Registry). United States National Library of Medicine. 28 May 2020. NCT04405908. Retrieved 14 July 2020.
- "Clover Biopharmaceuticals starts Phase I Covid-19 vaccine trial". Clinical Trials Arena. 20 June 2020. Retrieved 25 June 2020.
- "About Us". Clover Biopharmaceuticals. Retrieved 1 August 2020.
- "Monovalent Recombinant COVID19 Vaccine (COVAX19)". ClinicalTrials.gov (Registry). United States National Library of Medicine. 1 July 2020. NCT04453852. Retrieved 14 July 2020.
- "Vaxine". Retrieved 1 August 2020.
- "A Phase I clinical trial to evaluate the safety, tolerance and preliminary immunogenicity of different doses of a SARS-CoV-2 mRNA vaccine in population aged 18–59 years and 60 years and above". Chinese Clinical Trial Register (Registry). 24 June 2020. ChiCTR2000034112. Retrieved 6 July 2020.
- "Company introduction". Walvax Biotechnology. Retrieved 1 August 2020.
- "Safety, Tolerability and Immunogenicinity of a Coronavirus-Like Particle COVID-19 Vaccine in Adults Aged 18-55 Years". ClinicalTrials.gov (Registry). United States National Library of Medicine. 29 June 2020. NCT04450004. Retrieved 14 July 2020.
- St Philip E, Favaro A, MacLeod M (14 July 2020). "The hunt for a vaccine: Canadian company begins human testing of COVID-19 candidate". CTV News. Retrieved 14 July 2020.
- "About Us". Medicago. Retrieved 1 August 2020.
- Chander V (14 July 2020). "Canada's Medicago begins human trials of plant-based COVID-19 vaccine". National Post. Reuters. Retrieved 14 July 2020.
- "A Study on the Safety, Tolerability and Immune Response of SARS-CoV-2 Sclamp (COVID-19) Vaccine in Healthy Adults". ClinicalTrials.gov (Registry). United States National Library of Medicine. 3 August 2020. NCT04495933. Retrieved 4 August 2020.
- "Public statement for collaboration on COVID-19 vaccine development". World Health Organization. 13 April 2020. Archived from the original on 20 April 2020. Retrieved 20 April 2020.
- Gouglas D, Thanh Le T, Henderson K, Kaloudis A, Danielsen T, Hammersland NC, Robinson JM, Heaton PM, Røttingen JA (December 2018). "Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study". Lancet Global Health. 6 (12): e1386–96. doi:10.1016/S2214-109X(18)30346-2. PMC 7164811. PMID 30342925.
- Strovel J, Sittampalam S, Coussens NP, Hughes M, Inglese J, Kurtz A, et al. (1 July 2016). "Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start-up Companies". Assay Guidance Manual. Eli Lilly & Company and the National Center for Advancing Translational Sciences. PMID 22553881.
- DiMasi JA, Grabowski HG, Hansen RW (May 2016). "Innovation in the pharmaceutical industry: New estimates of R&D costs". Journal of Health Economics. 47: 20–33. doi:10.1016/j.jhealeco.2016.01.012. hdl:10161/12742. PMID 26928437. Archived from the original on 5 December 2019. Retrieved 21 April 2020.
- Kleinnijenhuis J, van Crevel R, Netea MG (January 2015). "Trained immunity: consequences for the heterologous effects of BCG vaccination". Transactions of the Royal Society of Tropical Medicine and Hygiene. 109 (1): 29–35. doi:10.1093/trstmh/tru168. PMID 25573107.
- de Vrieze J (23 March 2020). "Can a century-old TB vaccine steel the immune system against the new coronavirus?". Science. doi:10.1126/science.abb8297. S2CID 216359131.
- O'Neill LA, Netea MG (June 2020). "BCG-induced trained immunity: can it offer protection against COVID-19?". Nat. Rev. Immunol. 20 (6): 335–37. doi:10.1038/s41577-020-0337-y. PMC 7212510. PMID 32393823.
- Escobar LE, Molina-Cruz A, Barillas-Mury C (July 2020). "BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)". Proc. Natl. Acad. Sci. U.S.A. 117 (30): 17720–26. doi:10.1073/pnas.2008410117. PMC 7395502. PMID 32647056.
- Koti M, Morales A, Graham CH, Siemens DR (July 2020). "BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy". J Immunother Cancer. 8 (2): e001119. doi:10.1136/jitc-2020-001119. PMC 7342862. PMID 32636240.
- "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.
- "Reducing health care workers absenteeism in SARS-CoV-2 pandemic by enhanced trained immune responses through Bacillus Calmette-Guérin vaccination, a randomized controlled trial (COVID-19)". EU Clinical Trials Register (Registry). European Union. 17 March 2020. EudraCT 2020-000919-69. Archived from the original on 4 April 2020. Retrieved 11 April 2020.
- "Murdoch Children's Research Institute to trial preventative vaccine for COVID-19 healthcare workers". Murdoch Children's Research Institute. Archived from the original on 13 April 2020. Retrieved 11 April 2020.
- "BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE)". ClinicalTrials.gov (Registry). United States National Library of Medicine. 31 March 2020. NCT04327206. Archived from the original on 11 April 2020. Retrieved 11 April 2020.
- "Measles Vaccine in HCW (MV-COVID19)". ClinicalTrials.gov (Registry). United States National Library of Medicine. 22 April 2020. NCT04357028. Archived from the original on 7 May 2020. Retrieved 24 April 2020.
- Tregoning, John S.; Russell, Ryan F.; Kinnear, Ekaterina (25 January 2018). "Adjuvanted influenza vaccines". Human Vaccines and Immunotherapeutics. 14 (3): 550–64. doi:10.1080/21645515.2017.1415684. ISSN 2164-5515. PMC 5861793. PMID 29232151.
- Wang, Jieliang; Peng, Ying; Xu, Haiyue; Cui, Zhengrong; Williams, Robert O. (5 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. ISSN 1530-9932. PMC 7405756. PMID 32761294.
- Thorp HH (27 March 2020). "Underpromise, overdeliver". Science. 367 (6485): 1405. Bibcode:2020Sci...367.1405T. doi:10.1126/science.abb8492. PMID 32205459.
- "Ten health issues WHO will tackle this year". World Health Organization. 2019. Archived from the original on 11 November 2019. Retrieved 26 May 2020.
- Dubé E, Laberge C, Guay M, Bramadat P, Roy R, Bettinger J (1 August 2013). "Vaccine hesitancy: an overview". Human Vaccines and Immunotherapeutics. 9 (8): 1763–73. doi:10.4161/hv.24657. ISSN 2164-554X. PMC 3906279. PMID 23584253.
- Malik, Amyn A; McFadden, SarahAnn M; Elharake, Jad; Omer, Saad B (2020). "Determinants of COVID-19 vaccine acceptance in the US". EClinicalMedicine, the Lancet. 26: 100495. doi:10.1016/j.eclinm.2020.100495. ISSN 2589-5370. PMC 7423333. PMID 32838242.
- Linda Thunström, Madison Ashworth, David Finnoff, and Stephen C. Newbold. 2020. Hesitancy towards a COVID-19 vaccine and prospects for herd immunity. Covid Economics 35: 7 July 2020
- Iwasaki A, Yang Y (21 April 2020). "The potential danger of suboptimal antibody responses in COVID-19". Nature Reviews Immunology. 20 (6): 339–41. doi:10.1038/s41577-020-0321-6. ISSN 1474-1733. PMC 7187142. PMID 32317716.
- Wiedermann U, Garner-Spitzer E, Wagner A (2016). "Primary vaccine failure to routine vaccines: Why and what to do?". Human Vaccines and Immunotherapeutics. 12 (1): 239–43. doi:10.1080/21645515.2015.1093263. ISSN 2164-554X. PMC 4962729. PMID 26836329.
- Zumla A, Hui DS, Perlman S (11 September 2015). "Middle East respiratory syndrome". Lancet. 386 (9997): 995–1007. doi:10.1016/S0140-6736(15)60454-8. PMC 4721578. PMID 26049252.
- Garcia de Jesus E (26 May 2020). "Is the coronavirus mutating? Yes. But here's why you don't need to panic". Science News. Archived from the original on 21 June 2020. Retrieved 21 June 2020.
- 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.
- Winter, SS; Page-Reeves, JM; Page, KA; Haozous, E; Solares, A; Nicole Cordova, C; Larson, RS (28 May 2018). "Inclusion of special populations in clinical research: important considerations and guidelines". Journal of Clinical and Translational Research (Review). 4 (1): 56–69. ISSN 2382-6533. PMC 6410628. PMID 30873495.
- Gates B (23 April 2020). "The first modern pandemic: The scientific advances we need to stop COVID-19". The Gates Notes. Archived from the original on 13 May 2020. Retrieved 6 May 2020.
- Stevis-Gridneff M, Jakes L (4 May 2020). "World Leaders Join to Pledge $8 Billion for Vaccine as U.S. Goes It Alone". The New York Times. ISSN 0362-4331. Archived from the original on 13 May 2020. Retrieved 10 May 2020.
- Blanchfield M (30 April 2020). "Global philanthropists, experts call for COVID-19 vaccine distribution plan". The Toronto Star. Archived from the original on 7 May 2020. Retrieved 6 May 2020.
- "7 looming questions about the rollout of a Covid-19 vaccine". STAT. 9 October 2020. Retrieved 10 October 2020.
- Eyal N, Lipsitch M, Smith PG (31 March 2020). "Human challenge studies to accelerate coronavirus vaccine licensure". The Journal of Infectious Diseases. 221 (11): 1752–56. doi:10.1093/infdis/jiaa152. PMC 7184325. PMID 32232474. Archived from the original on 24 April 2020. Retrieved 19 April 2020.
- Callaway E (April 2020). "Should scientists infect healthy people with the coronavirus to test vaccines?". Nature. 580 (7801): 17. Bibcode:2020Natur.580...17C. doi:10.1038/d41586-020-00927-3. PMID 32218549. Archived from the original on 14 April 2020. Retrieved 19 April 2020.
- Boodman E (13 March 2020). "Coronavirus vaccine clinical trial starting without usual animal data". STAT. Archived from the original on 17 April 2020. Retrieved 19 April 2020.
- Cohen J (31 March 2020). "Speed coronavirus vaccine testing by deliberately infecting volunteers? Not so fast, some scientists warn". Science. doi:10.1126/science.abc0006. Archived from the original on 14 April 2020. Retrieved 19 April 2020.
- Walker P, Whittaker C, Watson O, Baguelin M, Ainslie K, Bhatia S, et al. (26 March 2020). "The global impact of COVID-19 and strategies for mitigation and suppression" (PDF). Imperial College COVID-19 Response Team. doi:10.25561/77735. Archived (PDF) from the original on 21 April 2020. Retrieved 19 April 2020. Cite journal requires
- "Key criteria for the ethical acceptability of COVID-19 human challenge studies" (PDF). World Health Organization. 6 May 2020. Archived (PDF) from the original on 8 May 2020. Retrieved 12 May 2020.
- "Principles and considerations for adding a vaccine to a national immunization programme" (PDF). World Health Organization. 1 April 2014. Retrieved 17 August 2020.
- Wijnans, Leonoor; Voordouw, Bettie (11 December 2015). "A review of the changes to the licensing of influenza vaccines in Europe". Influenza and Other Respiratory Viruses. 10 (1): 2–8. doi:10.1111/irv.12351. ISSN 1750-2640. PMC 4687503. PMID 26439108.
- Paul A. Offit (2020). "Making vaccines: Licensure, recommendations and requirements". Children's Hospital of Philadelphia. Retrieved 20 August 2020.
- Toner E, Barnill A, Krubiner C, others (19 August 2020). "Interim Framework for COVID-19 Vaccine Allocation and Distribution in the United States" (PDF). Baltimore, MD: Johns Hopkins University Center for Health Security. Retrieved 24 August 2020.
- "EMA starts first rolling review of a COVID-19 vaccine in the EU". European Medicines Agency (EMA) (Press release). 1 October 2020. Retrieved 1 October 2020.
- "COVID-19 vaccines: key facts". European Medicines Agency (EMA). 14 September 2020. Retrieved 1 October 2020.
- "EMA starts second rolling review of a COVID-19 vaccine". European Medicines Agency (EMA) (Press release). 5 October 2020. Retrieved 6 October 2020.
- "Vaccine product approval process". US Food and Drug Administration. 30 January 2020. Retrieved 17 August 2020.
- Corey, Lawrence; Mascola, John R; Fauci, Anthony S; Collins, Francis S (11 May 2020). "A strategic approach to COVID-19 vaccine R&D". Science. 368 (6494): 948–50. doi:10.1126/science.abc5312. ISSN 0036-8075. PMID 32393526.
- "WHO publishes Emergency Use Listing procedure and roadmap to make new medical products more readily available during health emergencies". World Health Organization. 9 January 2020. Retrieved 23 August 2020.
- "Vaccines: The Emergency Authorisation Procedure". European Medicines Agency. 2020. Retrieved 21 August 2020.
- "WHO 'backed China's emergency use' of experimental Covid-19 vaccines". South China Morning Post. 25 September 2020. Retrieved 26 September 2020.
- Kramer, Andrew E. (19 September 2020). "Russia Is Slow to Administer Virus Vaccine Despite Kremlin's Approval". The New York Times. ISSN 0362-4331. Retrieved 28 September 2020.
- "FDA may be risk-averse to grant emergency use for a Covid-19 vaccine; political pressure and hazy EUA standards are factors". ClinicalTrials Arena, Verdict Media, Ltd. 2 July 2020. Retrieved 22 August 2020.
- Jan Hoffman (18 July 2020). "Mistrust of a coronavirus vaccine could imperil widespread immunity". The New York Times. Retrieved 23 August 2020.
- "Biopharma leaders unite to stand with science". SANOFI. 8 September 2020.
- 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.
- "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.
- 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.
- Blankenship K (4 June 2020). "AstraZeneca unveils massive $750M deal in effort to produce billions of COVID-19 shots". FiercePharma. Archived from the original on 10 June 2020. Retrieved 8 June 2020.
- Cohen J (4 June 2020). "Top U.S. scientists left out of White House selection of COVID-19 vaccine short list". Science. doi:10.1126/science.abd1719. ISSN 0036-8075. Archived from the original on 9 June 2020. Retrieved 10 June 2020.
- Bollyky TJ, Gostin LO, Hamburg MA (7 May 2020). "The equitable distribution of COVID-19 therapeutics and vaccines". JAMA. 323 (24): 2462–63. doi:10.1001/jama.2020.6641. PMID 32379268. Archived from the original on 12 May 2020. Retrieved 10 June 2020.
- Aakash B, Faulconbridge G, Holton K (22 May 2020). "U.S. secures 300 million doses of potential AstraZeneca COVID-19 vaccine". The Guardian. Reuters. Archived from the original on 10 June 2020. Retrieved 10 June 2020.
- Paton J, Griffin R, Koons C. "U.S. likely to get Sanofi vaccine first if it succeeds". Bloomberg. Archived from the original on 8 June 2020. Retrieved 8 June 2020.
- Callaway, Ewen (27 August 2020). "The unequal scramble for coronavirus vaccines – by the numbers". Nature. 584 (7822): 506–07. Bibcode:2020Natur.584..506C. doi:10.1038/d41586-020-02450-x. PMID 32839593. S2CID 221285160.
- Khamsi R (9 April 2020). "If a coronavirus vaccine arrives, can the world make enough?". Nature. 580 (7805): 578–80. Bibcode:2020Natur.580..578K. doi:10.1038/d41586-020-01063-8. PMID 32273621. Archived from the original on 13 May 2020. Retrieved 10 June 2020.
- Gretler C (18 May 2020). "China pledges to make its coronavirus vaccine a 'public good'". The National Post. Bloomberg. Retrieved 9 June 2020.
- Huneycutt B, Lurie N, Rotenberg S, Wilder R, Hatchett R (24 February 2020). "Finding equipoise: CEPI revises its equitable access policy". Vaccine. 38 (9): 2144–48. doi:10.1016/j.vaccine.2019.12.055. PMC 7130943. PMID 32005536.
- "Vaccine for COVID-19". The Center for Artistic Activism. 22 March 2020. Archived from the original on 9 June 2020. Retrieved 8 June 2020.
- "UAEM response to COVID-19". Universities Allied for Essential Medicines. 2020. Archived from the original on 21 April 2020. Retrieved 9 June 2020.
- Ferrucci A. (05 MAY 2020). "More than 100 scientists call for Covid 19 vaccines to be in the public domain". edc.online.org. Retrieved July 21, 2020.
- "How the massive plan to deliver the COVID-19 vaccine could make history – and leverage blockchain like never before". World Economic Forum. 17 July 2020. Retrieved 16 September 2020.
- Brendan Murray and Riley Griffin (24 July 2020). "The world's supply chain isn't ready for a Covid-19 vaccine". Bloomberg World. Retrieved 13 September 2020.CS1 maint: uses authors parameter (link)
- Scott Duke Kominers; Alex Tabarrok (18 August 2020). "Vaccines use bizarre stuff. We need a supply chain now". Bloomberg Business. Retrieved 13 September 2020.
- "The time to prepare for COVID-19 vaccine transport is now". UNICEF. 10 September 2020. Retrieved 13 September 2020.
- Devika Desai (10 September 2020). "Transporting one single dose of COVID-19 vaccine could take up to 8,000 jumbo planes, says aviation body". National Post. Retrieved 13 September 2020.
The IATA estimated that 8,000 747 cargo planes, at minimum, would be needed to transport a single dose of the vaccine worldwide, but more equipment could be required as administering the vaccine might mean several doses. Vaccines would also have to be stored at a temperature range between two and eight degrees Celsius, which could rule out the use of some types of planes.
- Quelch, Rich (14 August 2020). "COVID-19 vaccine delivery – overcoming the supply chain challenges". PharmiWeb.com. Retrieved 13 September 2020.
Delivering a new vaccine for COVID-19 worldwide will be one of the greatest challenges faced by modern pharma. The difficulties are intensified by pre-existing shortcomings in the supply chain.
- Seidman, Gabriel; Atun, Rifat (2017). "Do changes to supply chains and procurement processes yield cost savings and improve availability of pharmaceuticals, vaccines or health products? A systematic review of evidence from low-income and middle-income countries". BMJ Global Health. 2 (2): e000243. doi:10.1136/bmjgh-2016-000243. ISSN 2059-7908. PMC 5435270. PMID 28589028.
- "172 countries and multiple candidate vaccines engaged in COVID-19 Vaccine Global Access Facility". GAVI. 4 September 2020. Retrieved 15 September 2020.
- "UNICEF to lead procurement and supply of COVID-19 vaccines in world's largest and fastest ever operation of its kind". UNICEF. 4 September 2020. Retrieved 15 September 2020.
- Emily Cook (4 September 2020). "UNICEF to lead supply chain for COVID-19 vaccine". Manufacturing. Retrieved 13 September 2020.
- Hessel, Luc (2009). "Pandemic influenza vaccines: meeting the supply, distribution and deployment challenges". Influenza and Other Respiratory Viruses. 3 (4): 165–70. doi:10.1111/j.1750-2659.2009.00085.x. ISSN 1750-2640. PMC 4634681. PMID 19627373.
- "Vaccine management and logistics support". World Health Organization. 2020. Retrieved 14 September 2020.
- Jarrett, Stephen; Yang, Lingjiang; Pagliusi, Sonia (9 June 2020). "Roadmap for strengthening the vaccine supply chain in emerging countries: Manufacturers' perspectives". Vaccine X. 5: 100068. doi:10.1016/j.jvacx.2020.100068. ISSN 2590-1362. PMC 7394771. PMID 32775997.
- Lloyd, John; Cheyne, James (2017). "The origins of the vaccine cold chain and a glimpse of the future". Vaccine. 35 (17): 2115–20. doi:10.1016/j.vaccine.2016.11.097. ISSN 0264-410X. PMID 28364918.
- "How can we make enough vaccine for 2 billion people?". World Economic Forum. 25 August 2020. Retrieved 16 September 2020.
- "Coronavirus vaccine pre-orders worldwide top 5 billion". The Japan Times. 12 August 2020. Retrieved 13 September 2020.
- C, Hannah (10 October 2020). "China Commits to Producing 600 Million Vaccine Doses by the End of 2020". Science Times. Retrieved 10 October 2020.
- Megan Molteni (26 June 2020). "Vaccine makers turn to microchip tech to beat glass shortages". Wired. Retrieved 17 September 2020.
- Fraiser Kansteiner (8 July 2020). "With COVID-19 vaccines coming, SiO2 injects $163M into vial production plant". FiercePharma, Questex LLC. Retrieved 17 September 2020.
- Ludwig Burger; Matthias Blamont (11 June 2020). "Bottlenecks? Glass vial makers prepare for COVID-19 vaccine". Reuters. Retrieved 17 September 2020.
- Deborah Abrams Kaplan (7 July 2020). "3 applications for RFID in the fight against COVID-19". Supply Chain Dive. Retrieved 17 September 2020.
- Kartoglu, Umit; Milstien, Julie (28 May 2014). "Tools and approaches to ensure quality of vaccines throughout the cold chain". Expert Review of Vaccines. 13 (7): 843–54. doi:10.1586/14760584.2014.923761. ISSN 1476-0584. PMC 4743593. PMID 24865112.
- Hanson, Celina M.; George, Anupa M.; Sawadogo, Adama; Schreiber, Benjamin (19 April 2017). "Is freezing in the vaccine cold chain an ongoing issue? A literature review". Vaccine. 35 (17): 2127–33. doi:10.1016/j.vaccine.2016.09.070. ISSN 0264-410X. PMID 28364920.
- Elizabeth Weise (6 September 2020). "'Mind-bogglingly complex': Here's what we know about how COVID-19 vaccine will be distributed when it's approved". USA Today. Retrieved 13 September 2020.
- Madhav Durbha (29 June 2020). "The extra mile: preparing a supply chain for a COVID-19 vaccine". European Pharmaceutical Review. Retrieved 13 September 2020.
- "The time to prepare for COVID-19 vaccine transport is now". International Air Transport Association. 9 September 2020. Retrieved 13 September 2020.
- "COVID-19-related trafficking of medical products as a threat to public health" (PDF). United Nations Office on Drugs and Crime. 2020. Retrieved 16 September 2020.
- Kohler, Jillian Clare; Dimancesco, Deirdre (3 February 2020). "The risk of corruption in public pharmaceutical procurement: how anti-corruption, transparency and accountability measures may reduce this risk". Global Health Action. 13 (sup1): 1694745. doi:10.1080/16549716.2019.1694745. ISSN 1654-9716. PMC 7170361. PMID 32194011.
- Samanth Subramanian (13 August 2020). "Biometric tracking can ensure billions have immunity against Covid-19". Bloomberg Businessweek. Retrieved 16 September 2020.
- "Effective Vaccine Management (EVM) Initiative:Vaccine Management Handbook". World Health Organization. 9 September 2020. Retrieved 16 September 2020.
- Azar A (4 February 2020). "Notice of Declaration under the Public Readiness and Emergency Preparedness Act for medical countermeasures against COVID-19". Archived from the original on 25 April 2020. Retrieved 22 April 2020.
- Kertscher T (23 January 2020). "No, there is no vaccine for the Wuhan coronavirus". PolitiFact. Poynter Institute. Archived from the original on 7 February 2020. Retrieved 7 February 2020.
- McDonald J (24 January 2020). "Social Media Posts Spread Bogus Coronavirus Conspiracy Theory". FactCheck.org. Annenberg Public Policy Center. Archived from the original on 6 February 2020. Retrieved 8 February 2020.
- "Warning Letter – North Coast Biologics – MARCS-CMS 607532". U.S. Food and Drug Administration (FDA). 21 May 2020. Archived from the original on 26 May 2020. Retrieved 23 May 2020.
- Funk CD, Laferrière C, Ardakani A (2020). "A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic". Front Pharmacol. 11: 937. doi:10.3389/fphar.2020.00937. PMC 7317023. PMID 32636754.
- Johnson CY, Mufson S (11 June 2020). "Can old vaccines from science's medicine cabinet ward off coronavirus?". The Washington Post.
- Zimmer C, Sheikh K, Weiland N (20 May 2020). "A New Entry in the Race for a Coronavirus Vaccine: Hope". The New York Times.
- "Development and Licensure of Vaccines to Prevent COVID-19" (PDF). U.S. Food and Drug Administration (FDA). June 2020. Lay summary.
- "Coronavirus Vaccine Tracker". The New York Times.
- COVID-19 vaccine tracker, Regulatory Focus
- "STAT's Covid-19 Drugs and Vaccines Tracker". Stat.
- "Biopharma Leaders Unite to Stand with Science" (Press release). 8 September 2020 – via Business Wire.
- "Protocol mRNA-1273-P301" (PDF). Moderna.
- "Protocol C4591001 PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)" (PDF). Pfizer.
- "Protocol AZD1222 – D8110C00001" (PDF). AstraZeneca.
- "Protocol VAC31518COV3001; Phase 3" (PDF). Janssen Vaccines & Prevention.