• There are almost 150 coronavirus vaccine candidates under development. Only 19 of these are now being tested in humans.

  • Many types of vaccines are rapidly progressing through clinical trials. Only two vaccine candidates have announced large scale Phase 3 trials, involving several thousands of people. Only one candidate has been approved for restricted human use.

  • Measuring a reduction in COVID-19 levels is an obstacle for Phase 3 clinical trials, as they require a high infection rate among the tested population to prove vaccine efficacy. International agreements with countries where SARS-CoV-2 infection rates are still high are facilitating those trials.

  • Future challenges in vaccine development include a better understanding of COVID-19 immunity and development of vaccination strategies.

  • This is part of our rapid response content on COVID-19. You can view all our reporting on this topic under COVID-19.

Fast-track development and investment for vaccines against SARS-CoV-2 started soon after the publication of its genetic sequence in January. So far, the UK Government has pledged £250m to the Coalition for Epidemic Preparedness Innovations (CEPI) for the development of a coronavirus vaccine and has announced the equivalent of £330m a year over the next 5 years to Gavi, the Vaccine Alliance. This fund will contribute to the vaccination of up to 75 million children against preventable diseases (like measles or polio) in developing countries, supporting the recovery of their health systems following the COVID-19 pandemic. On 4 June, the UK hosted the Global Vaccine Summit, where the Gavi Advance Market Commitment for COVID-19 Vaccines (Gavi Covax AMC) was launched. This project aims to ensure the access to COVID-19 vaccines for low- and middle-income countries and received more than US$0.5 billion in initial seed money during the Summit.

In this article we use the term ‘vaccine candidate’ to indicate a vaccine yet to be approved for commercial use in humans. As of 6 July 2020, the latest WHO figures show almost 150 vaccine candidates in development across the world, 19 of which are currently being tested in humans. In the past few weeks, vaccine candidates have been rapidly progressing through the first two phases of clinical trials (Phase 1 and Phase 2). These trials test safety and if they stimulate an immune response in people.

Coronavirus vaccine tracker, showing vaccine candidates at different stages. Vaccine candidates are counted at the most advanced stage they are at, such that Phase 1/2 combined trials are counted as Phase 2 trials. Phase 3 trials are ongoing only for the vaccine candidate developed by the Jenner Institute (University of Oxford) and the Oxford Vaccine Group. Other two candidates (developed by the Chinese companies Sinopharm and Sinovac) have just received approval for Phase 3 trials. Adapted from New York Times. Image updated as of 6 July 2020.

Vaccine technologies

There are different types of vaccine, which differ in how they are made or how they stimulate the immune system. Several approaches are being developed and tested in people for SARS-CoV-2:

The different strategies in use have complementary advantages and disadvantages. For example, inactivated vaccines (such as most poliovirus or influenza virus vaccines) are effective, but they usually require difficult manufacturing processes and multiple doses to stimulate an immune response. DNA- and RNA-based vaccines are cheaper, more stable, and easier to manufacture, but no vaccines based on this technology have been approved for human use yet.

Developing multiple SARS-CoV-2 candidates could facilitate large-scale production and immunisation programmes across the world. For example, some candidates could be used as an initial dose to ‘prime’ the immune system, and others can be used afterwards as immunisation boosters, to help develop a protective immune response (this is known as the ‘prime and boost’ immunisation strategy). However, experts warn that success rates for vaccine development are extremely low. Therefore, the greater the variety of approaches, the more it likely is to find one or multiple successful candidates.

Which candidates are further ahead?

Four candidates are leading the race for a SARS-CoV-2 vaccine:

The University of Oxford has also established a partnership with the pharmaceutical company AstraZeneca to ensure further development, large-scale manufacture and distribution if their vaccine is effective. Since May, the company has concluded several agreements to ensure vaccine supply at no profit during the pandemic. These include agreements for 100m doses in the UK and 300m doses in the US, as well as agreements with CEPI, Gavi, the Serum Institute of India and a 400m dose agreement with Europe’s Inclusive Vaccines Alliance.

Other key advances worldwide:

Worldwide, Phase 1 and Phase 2 trials have progressed for a series of vaccine candidates.

Other vaccine candidates, such as the Gamaleya Research Institute candidate and the Genexine candidate, started Phase 1 trials in the last few weeks.

Future challenges

Phase 3 trials require the vaccine candidate to be tested on several thousand people under natural disease conditions, with the virus able to circulate among the population. These studies allow testing of the candidate’s efficacy to protect against SARS-CoV-2 infection and identify rare side effects. This is difficult if the rate of SARS-CoV-2 infections in the general population is low, which is now the case in some countries. This means that Phase 3 trials have to be carried out in countries or regions with high rates of infection, such as the US and Brazil. The alternative is to intentionally infect participants with the virus in order to test how effective a vaccine is, but this raises significant ethical concerns. International agreements to test vaccine candidates under natural disease conditions are facilitating Phase 3 trials:

The overarching challenge in SARS-CoV-2 vaccine development is that the immune response and its duration is still not fully understood (see Immunity to COVID-19). Concerns shared among experts include the maintenance of long-lasting immunity (which requires the immune system to recognise and kill the virus months after being exposed to it) and the development of vaccination strategies. During a recent oral evidence session of the House of Lords Science and Technology Committee, experts suggested that a possible immunisation strategy could involve the targeted vaccination of groups, an approach used for influenza. This would confer population-level protection for at-risk individuals, who are less likely to develop a good immune response to a vaccine.

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