After a novel coronavirus pneumonia was detected in December 2019the genetic sequence of COVID‑19 was published on 11 January 2020, triggering an urgent international response to prepare for the outbreak and hasten development of a preventative vaccine. 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, becine for an infectious disease has never before been produced in less than several years, and no vaccine exists for preventing a coronavirus infection in human. As of April, CEPI estimates that as many as six of the 115 vaccine candidates against COVID‑19 should be chosen by international coalitions for development through Phase II–III trials, and three should be streamlined through regulatory and quality assurance for eventual licensing at a total cost of at least US$2 billion.Another analysis estimates 10 candidates will need simultaneous initial development, before a select few are chosen for the final path to licensing.
The vaccine effort is being prioritized for speed of rigorous clinical evaluation for safety and efficacy, financing, and planning to manufacture billions of doses, and eventual worldwide deployment and equitable access among developed and undeveloped countries.WHO, CEPI, and the Gates Foundation are committing money and organizational resources for the prospect that several vaccines will be needed to prevent continuing COVID‑19 infection.The vaccines will require custom formulation, special packaging, transportation, and storage in all 200 countries with infected citizens.The WHO estimates a total cost of US$8 billion to develop a suite of three or more vaccines having different technologies and distribution to prevent COVID‑19 infections worldwide.
International organizations
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 an Access to COVID‑19 Tools Accelerator for coordinating global vaccine development. 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.
The Coalition for Epidemic Preparedness Innovations (CEPI) is working with international health authorities and vaccine developers to create another US$8 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 three 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 specific funding of research priorities needed for a COVID‑19 vaccine, coordinating among the international funding and research organizations to maintain updated information on vaccine progress and avoid duplicate funding. 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
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 vaccine developers through its central bank, and has enabled land trans 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.
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 taskforce 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.
US Government Accountability Office diagram coparing a traditional vaccine development timeline to a possible expedited timeline
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.
Partnerships and competition
WHO Solidarity trial
The WHO, with a multinational coalition of vaccine scientists, has developed 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.combine financial and manufacturing capabilities for a pandemic adjuvant technology, GSK joined with Sanofi in an uncommon partnership of multinational companies to support accelerated vaccine development.
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 count 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 three or more 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.Both the WHO and CEPI have discussed concerns that affluent countries should not have priority access to the global supply of eventual COVID‑19 vaccines.
Allegations of Russian espionage
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) have warned that Russian state-backed hackers have been trying to steal COVID-19 treatment and vaccine research from academic and pharmaceutical institutions in other countries; Russia has denied it.
Compressed timelines
Geopolitical issues, safety concerns for vulnerable populations, and manufacturing challenges for producing billions of doses are compressing schedules to shorten the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process typically conducted sequentially over years.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. If a vaccine fails in development, not providing adequate prevention against the virus – data show that 84–90% of vaccine candidates fail (have "attrition") in Phase III clinical trials 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.
Technology platforms
In April, CEPI scientists reported that ten different technology platforms were under research and development during early 2020 to create an effective vaccine against COVID‑19.According to CEPI, the platforms based on DNA or messenger RNA, i.e. DNA vaccines or RNA vaccines, offer considerable promise to alter COVID‑19 antigen functions for strong immune responses, and can be rapidly assessed, refined for long-term stability, and prepared for large-scale production capacity. Other platforms being developed in 2020 focus on non-replicating viral vectors, peptides, recombinant proteins, live attenuated viruses, and inactivated viruses.
In general, the vaccine technologies being developed for COVID‑19 are not like vaccines already in use to prevent influenza, but rather are using "next-generation" strategies for precision on the COVID‑19 infection mechanisms, while hastening development for eventually preventing infection with a new vaccine. Vaccine platforms in development are also designed to address mechanisms for infection susceptibility to COVID‑19 in specific population subgroups, such as the elderly, children, pregnant women, and people with existing weakened immune systems.
These landscape documents have been prepared by the World Health Organization (WHO) for information purposes only concerning the 2019-2020 global of the novel coronavirus. Inclusion of any particular product or entity in any of these landscape documents does not constitute, and shall not be deemed or construed as, any approval or endorsement by WHO of such product or entity (or any of its businesses or activities). While WHO takes reasonable steps to verify the accuracy of the information presented in these landscape documents, WHO does not make any (and hereby disclaims all) representations and warranties regarding the accuracy, completeness, fitness for a particular purpose (including any of the aforementioned purposes), quality, safety, efficacy, merchantability and/or non-infringement of any information provided in these landscape documents and/or of any of the products referenced therein. WHO also disclaims any and all liability or responsibility whatsoever for any death, disability, injury, suffering, loss, damage or other prejudice of any kind that may arise from or in connection with the procurement, distribution or use of any product included in any of these landscape documents.
A COVID‑19 vaccine is a biotechnology product intended to provide acquired immunity against coronavirus disease 2019 (COVID‑19). As of August 2020, there were 231 vaccine candidates in development, although no candidate has completed clinical trials to prove its safety and efficacy. In August, at least 25 vaccine candidates were in clinical trials, with six beginning Phase III and 19 still in Phase
Previous work to develop a vaccine against the coronavirus diseases SARS and MERS established considerable knowledge about the structure and function of coronaviruses – which accelerated rapid development during early 2020 of varied technology platforms for a COVID‑19 vaccine.
The Coalition for Epidemic Preparedness Innovations (CEPI), which is organizing a US$2 billion worldwide fund for rapid investment and development of vaccine candidates, indicated in April that a vaccine may be available under emergency use protocols in less than twelve months or by early 2021.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.
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.
Vaccines have been produced against several animal diseases caused by coronaviruses, including 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 SARSand MERShave been tested in non-human animal models.
For SARS, as of 2020 there is no cure or protective vaccine that has been shown to be both safe and effective in humans.According to research papers published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world at that time.
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).