A review published in the BSI’s journal Clinical & Experimental Immunology explores the immune response required to protect against the novel coronavirus SARS-CoV-2 and the different approaches being used to develop vaccines for COVID-19.
The novel coronavirus SARS-CoV-2, which causes COVID-19, emerged in December 2019. Scientific research began immediately on vaccine development and sixty‐three days after the SARS‐CoV‐2 genetic sequence was made public, the first doses of the first human vaccine were being tested. This review summarises the vaccine landscape up until 24 September 2020, including those vaccines being tested in clinical trials.
The immune response to SARS-CoV-2
Because SARS-CoV-2 is a new virus there is a still a lot to be learnt about the natural immune response and if protective immunity is generated, how long it lasts for. It’s hoped that vaccines will produce a better immune response than the virus itself, but this is yet to be determined. It has become apparent that the T cell response as well as the antibody response is important to control infection with SARS-CoV-2 and protect from reinfection.
Understanding the immune response to SARS-CoV-2 will be critical for vaccine safety. Vaccines can induce some side effects, mostly pain at the injection site, a headache and in some people a short increase in temperature. Testing the safety of potential vaccines is a critical part of the clinical trials, as is ongoing monitoring after the vaccine has been rolled out.
Vaccines against SARS-CoV-2 in clinical trials
Each type of vaccine being developed needs to consider which antigen it targets. An antigen is a unique feature of the virus, usually a protein on its surface, which triggers an immune response. In the case of SARS-CoV-2, most vaccines target the spike protein which is responsible for allowing the virus to attach to and enter human cells and produces an antibody response. There are other possible antigens that also stimulate antibodies or the T cell response.
There are a wide range of approaches being used to develop a vaccine against SARS-CoV-2. They can be summarised into the following categories:
- Protein vaccines: This group of vaccines use a surface protein antigen from the virus to induce an immune response. The protein is made in a host cell using the viral genetic code. These types of vaccines have good safety records but usually need to be administered with an adjuvant, which is a substance added to help create a stronger immune response to the vaccine. Subsets of protein vaccines include nanoparticles and virus‐like particles, which are artificially produced nanoparticles that resemble the virus and peptide vaccines, which use only a fragment of the entire protein antigen. Artificial antigen-presenting cells are an immunotherapy used to stimulate T cell responses, which have been explored for cancer vaccines but seem impractical for mass vaccination campaigns.
- Inactivated vaccines: This group of vaccines use the whole virus which has been killed, usually by exposure to chemicals, and is safe to introduce to the immune system to induce a response. These vaccines may need the addition of an adjuvant.
- Live vaccines: This group of vaccines use the live virus and is the oldest vaccine approach. Live attenuated vaccines use a weakened form of the virus and induce an immune response that closely resembles the natural infection, meaning they may only need one dose and do not require an adjuvant, but the method requires time and extensive testing.
- Vectored vaccines are delivered in a vector constructed from a genetically modified harmless virus. The vectors can either be replicating, reproducing at the site of vaccination or be non-replicating, delivering the genetic material but not growing themselves. The vector contains a DNA molecule as a vehicle to introduce genetic material of the viral antigen protein to the immune system. When the vaccine is given, the body’s cells use the genetic material to produce the antigen protein, which is then recognised by the immune system as ‘foreign’ and induces an immune response. The Oxford/ AstraZeneca vaccine is a vectored vaccine, using a Chimpanzee adenovirus (or ChAd)
- Nucleic acid vaccines: This group of vaccines use the DNA (double stranded) or RNA (single stranded) genetic material that codes for the target antigen protein on the virus. The body’s cells produce the virus protein from the DNA or RNA and an immune response is induced. Nucleic acid vaccines are low cost and can potentially be developed rapidly but there isn’t currently any nucleic acid vaccine approved for human use. The Pfizer/BioNTech and Moderna vaccines that recently reported positive results are both RNA vaccines.
With a number of vaccines showing promising results in efficacy studies, the next stage is licensing the vaccine and then rolling them out in mass vaccine campaigns. However, there are many considerations before rolling out a global vaccination campaign. Clinical trials during the pandemic have been sped up due to increased cooperation between research ethics committees and regulatory agencies but have always ensured full safety data is collected and monitored. Manufacturing enough doses will be a challenge with key considerations around access to components and availability of manufacturing facilities. Any new vaccine will also require regulation and licensing through national and international agencies.
Worldwide collaboration will be vital to control COVID-19 and lessons will be learnt from this pandemic that will be invaluable for future outbreaks. It’s still too early to know what the best approach for a COVID-19 vaccine will be and important questions remain regarding what a successful vaccine looks like, how it should be deployed and who should be prioritised.
The development of a vaccine for COVID-19 is fast-moving and this summary and article were accurate at the time of publishing in September 2020.
Tregoning, J.S., Brown, E.S., Cheeseman, H.M., Flight, K.E., Higham, S.L., Lemm, N.‐M., Pierce, B.F., Stirling, D.C., Wang, Z. and Pollock, K.M. (2020), Vaccines for COVID‐19. Clinical & Experimental Immunology, 202: 162-192. https://doi.org/10.1111/cei.13517
First published 15 September 2020
Summary author Erika Aquino, BSI Public Engagement Manager