Research studies involving thousands of people have allowed scientists to test which drugs are effective at treating COVID-19. Several drug therapies are now available to treat people who are in hospital with COVID-19, or to prevent infections in vulnerable people becoming more serious. This briefing explains which drugs are available, the groups of people in which they are used and how they work. It also outlines the importance of monitoring the emergence of new variants and drug resistance.
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.
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:
- Inactivated vaccines, where the virus has been killed and therefore cannot multiply in the human body. This strategy is used by half (four of eight) of the Chinese vaccine candidates in clinical trials, including the Wuhan Institute of Biological Products/Sinopharm candidate and the Sinovac candidate CoronaVac.
- Protein-based vaccines, which contain a spike-shaped protein found on the surface of SARS-CoV-2 that is used to trigger the immune response, such as in the Novavax candidate and the Clover/GSK/Dynavax candidate.
- Adenovirus-based vaccines, where a harmless virus has been modified to contain the genetic information of the SARS-CoV-2 spike protein. Following vaccination, the body will produce this protein and develop an immune response against it. This strategy is used by the Jenner Institute (University of Oxford)/Oxford Vaccine Group candidate, by the Chinese CanSinoBIO/Academy of Military Medical Sciences candidate, and the Russian Gamaleya Research Institute candidate.
- DNA-based vaccines, where the genetic instructions to build the SARS-CoV-2 spike protein are directly injected into the human body, such as in the US-based Inovio candidate or the Korean Genexine candidate;
- RNA-based vaccines, containing more ‘ready-to-read’ instructions of the spike protein, that can be directly produced by the human body – this strategy is used by the Imperial College London candidate, the US National Institute of Allergy and Infectious Diseases (NIAID)/Moderna candidate and the BioNTech/Fosun Pharma/Pfizer BNT162 candidate.
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:
- On 25 June, the adenovirus-based candidate developed by CanSinoBIO and the Chinese Academy of Military Medical Sciences has been approved for military use in China for a year. On 22 May, results of Phase 1 trials, conducted in 108 healthy participants who were given different doses of the vaccine, were published.
- At the end of April, the Jenner Institute (University of Oxford) and the Oxford Vaccine Group completed Phase 1 vaccinations of over 1,000 healthy adults aged between 18 and 55 years. More than 10,000 participants across the UK and 30,000 in the US are currently being enrolled for Phase 2/3 clinical trials. Results from a preclinical trial in pigs, announced on 23 June, revealed that two doses of the vaccine (the ‘prime and boost’ strategy) produce a higher antibody response than a single dose.
- The Chinese company Sinopharm announced the approval of Phase 3 clinical trials of its inactivated vaccine candidate developed in collaboration with the Wuhan Institute of Biological Products.
- The Chinese company Sinovac is preparing for Phase 3 clinical trials in healthcare professionals. Their vaccine candidate CoronaVac will be tested on adults (18–59 years old) and older volunteers (60 years old and above). On 13 June, they announced positive preliminary results of Phase 1/2 trials in 743 healthy volunteers, aged 18 to 59 years.
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.
- On 18 May, the US company Moderna announced initial positive results from its Phase 1 trials. Phase 2 trials, with 600 healthy participants, have begun. On June 11, Moderna announced that it has completed production of the doses required for Phase 3 studies, expected to start in July with 30,000 participants.
- At the end of April, the US company Inovio completed enrolment of participants in Phase 1 trials. On June 30, they announced initial positive results from these studies. Preclinical models showed a robust immune response and Phase 2/3 trials are planned for July/August.
- Phase 1 trials of the BioNTech/Fosun Pharma/Pfizer candidate started in Germany on 23 April and in the US on 5 May. On 1st July they announced positive preliminary results from the US trial.
- At the end of May, the US company Novavax announced the beginning of Phase 1 trials. These will enrol 130 healthy participants aged 18 to 59 years in two Australian locations. Results are expected in July.
- In mid-June, Imperial College London announced the beginning of Phase 1 trials of its self-amplifying RNA vaccine candidate. This candidate is able to produce multiple copies of itself once injected in the human body, inducing an immune response with very small doses. The project has received a total investment of £41m from the UK Government and over £4m in philanthropic donations. Phase 1 trials will include 300 healthy participants, who will receive two doses of the vaccine candidate. This is the first time that self-amplifying RNA technology will be tested in humans. Phase 2 trials, involving 6,000 people, are planned for October.
- Imperial College London, in partnership with the life sciences investor Morningside Ventures, has founded the social enterprise VacEquity Global Health to distribute the vaccine at low cost for the UK and low-income countries, and the start-up company VaXEquity, to further develop its technologies for other diseases beyond the current pandemic.
- On 24 February, the UK-based company GSK started a partnership with the Chinese company Clover Biopharmaceuticals to develop a protein-based vaccine. On 23 June they announced the beginning of Phase 1 clinical trials in Australia. Results are expected in August.
Other vaccine candidates, such as the Gamaleya Research Institute candidate and the Genexine candidate, started Phase 1 trials in the last few weeks.
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:
- On 2 June, the Brazilian Health Regulatory Agency approved the inclusion of Brazil in Phase 3 clinical trials of the Oxford University/AstraZeneca candidate. The first volunteers were dosed on 24 June.
- On 11 June, Sinovac announced a collaboration with the Brazilian Instituto Butantan to conduct Phase 3 studies on its candidate CoronaVac.
- On 23 June, Phase 3 trials of the Oxford University/AstraZeneca candidate were announced to start in South Africa.
- On 24 June, Sinopharm reached an agreement with the United Arab Emirates to conduct Phase 3 trials of the candidate developed in collaboration with the Wuhan Institute of Biological Products.
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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