22 June 2020

Coronavirus: The search for a vaccine

 

Coronavirus
The novel coronavirus severe acute respiratory syndrome 2 (SARS-CoV-2) was first reported in Wuhan (the capital of Hubei province), China, in December 2019. Coronavirus disease 2019 (COVID‑19), which is caused by the SARS-CoV-2 virus, has a varied clinical pattern, from mild asymptomatic cases to cases of severe respiratory illness that require intensive care treatment [1]. Since the initial outbreak in Wuhan, the virus has spread rapidly across the globe, with the World Health Organization (WHO) declaring the outbreak a pandemic on 11 March 2020 [2]. By the beginning of June 2020, there were over six million confirmed cases of COVID‑19 and over 371,000 deaths worldwide [3].

Vaccines
Vaccines work by priming the body’s immune response to a pathogen (a virus or a bacterium) that it has not previously been exposed to [4]. Vaccines contain antigens (substances belonging to viruses and bacteria), which generate an immune response and cause the production of antibodies when introduced to the body. The production of antibodies primes the immune system to recognise and fight off future infections from that particular virus or bacterium [4, 5].

It is hoped that a vaccine against COVID-19 can be developed to reduce the spread of the virus and allow life to return to normal [1]. However, vaccine development is a complex, expensive and lengthy process; the typical success rate for vaccine development is just 6% and the average time taken to develop a vaccine is 10 years [6, 7].

Current research
There is currently a large undertaking of research into the development of a vaccine for SARS-CoV-2, with over 90 institutions carrying out research worldwide [8]. Several different types of vaccine are currently under development, including inactivated viral vaccines, subunit vaccines, mRNA vaccines, DNA vaccines and recombinant viral vector vaccines. There are currently 10 clinical trials for a possible SARS-CoV-2 vaccine underway in numerous countries, including the UK, the USA, Germany, France and China [1, 7, 9].

Inactivated viral vaccines have been used for many years and use a chemically inactivated version of a virus to generate an immune response [5, 10]. Sinovac Biotech is currently carrying out Phase I trials of their inactivated viral vaccine for COVID-19 [11]. Subunit vaccines are another type of commonly used vaccine; instead of using the entire virus, these vaccines typically use a protein, sugar, or a section from­ the surface of the virus to generate an immune response [5, 9, 10]. Clover Biopharmaceuticals collaboratively with GlaxoSmithKline is currently developing this type of vaccine based on the spike protein of SARS-CoV-2 [9]. The spike protein is an important target for vaccines because it is thought to play a key role in allowing the virus to bind to and enter host cells [5, 9, 10].

The Oxford Vaccine Group and Oxford’s Jenner Institute in the UK have started Phase I–II trials with the ChAdOx1 nCoV-19 vaccine. The vaccine is a viral vector vaccine that works by transferring genetic material from the virus of interest (in this case the genetic sequence of the spike protein from SARS-COV-2) into a non-pathogenic virus [9, 12]. This harmless virus is then introduced into the body and an immune response to the genetic material of the virus of interest is generated; a strong immune response can be generated from a single dose [10,12]. A recombinant viral vector vaccine has also been developed in China by CanSino Biologics in collaboration with the Academy of Military Medical Sciences and is currently undergoing a Phase II trial [1, 13, 14].

Additional clinical trials are assessing the possibility of mRNA and DNA vaccines, which are both newly developed types of vaccines not yet used in humans. mRNA vaccines work by introducing an mRNA sequence into the host cell that encodes a disease-specific antigen in order to generate the production of such antigens and consequently an immune response. [15–17].Moderna, is currently coordinating a Phase I clinical trial of an mRNA vaccine that uses synthetic lipid nanoparticles to carry mRNA templates of the SARS-CoV-2 spike protein into host cells [1]. Pfizer and biotech partner BioNTech SE have also started Phase I–II trials of an mRNA-based vaccine for SARS-CoV-2 [16].

DNA vaccines involve the injection of plasmids (extrachromosomal rings of DNA that can replicate autonomously) encoding a disease‑specific antigen into the body. Once the plasmids are injected into the body, the antigen is expressed and an immune response is generated [9, 10, 18, 19]. Currently, Inovio Pharmaceuticals is carrying out Phase I–II trials in its development of a DNA vaccine for COVID-19 [20].

The effects of the COVID-19 pandemic have been felt worldwide. Many academic institutes, pharmaceutical companies and biotechnology companies are now all working to develop a vaccine, and there are currently multiple different types of vaccines undergoing early clinical trials in humans. Both well established and emerging technology platforms have been utilised in the hunt for a vaccine, but it remains to be seen if, and when, these will be successful.

 

References

  1. Triggle CR, Bansal D, Farag EABA et al. COVID-19: Learning from lessons to guide treatment and prevention interventions. mSphere 2020; 5 (3): e00317–e00
  2. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 91(1): 157‐160.
  3. World Health Organization. WHO coronavirus disease (COVID-19) dashboard. Available at: https://covid19.who.int/. Accessed June 2020.
  4. Oxford Vaccine Group. What is a vaccine, and how do vaccines work? Available at: https://vk.ovg.ox.ac.uk/vk/how-do-vaccines-work. Accessed June 2020.
  5. How vaccines work. Available at: https://www.publichealth.org/public-awareness/understanding-vaccines/vaccines-work/. Accessed June 2020.
  6. European Vaccine Initiative. Stages of vaccine development. Available at: http://www.euvaccine.eu/vaccines-diseases/vaccines/stages-development. Accessed June 2020.
  7. Mullard A. COVID-19 vaccine development pipeline gears up. Lancet 2020; 395 (10239): 1751–
  8. Yang L, Tian D and Liu W. Strategies for vaccine development of COVID-19. Sheng Wu Gong Cheng Xue Bao 2020; 36 (4): 593–604.
  9. Ahn DG, Shin HJ, Kim MH et al. Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol 2020; 30 (3): 313–324.
  10. National Institute of Allergy and Infectious Diseases. Vaccine types. Available at: https://www.niaid.nih.gov/research/vaccine-types. Accessed June 2020.
  11. COVID-19 vaccine protects monkeys from new coronavirus, Chinese biotech reports. Available at: https://www.sciencemag.org/news/2020/04/covid-19-vaccine-protects-monkeys-new-coronavirus-chinese-biotech-reports. Accessed June 2020.
  12. University of Oxford: COVID-19 Oxford Vaccine Trial. About the COVID-19 vaccine trials. Available at: https://covid19vaccinetrial.co.uk/about. Accessed June 2020.
  13. Pipeline. Available at: http://www.cansinotech.com/homes/article/plist/45. Accessed June 2020.
  14. CanSinoBIO’s investigational vaccine against COVID-19 approved for Phase1 clinical trial in China. Available at: http://www.cansinotech.com/homes/article/show/56/153.html. Accessed June 2020.
  15. Pharmaceutical Technology. Could an innovative mRNA-based vaccine win the race for a Covid‑19 vaccine? Available at: https://www.pharmaceutical-technology.com/comment/covid-19-mrna-based-vaccine/. Accessed June 2020.
  16. gov. Study to describe the safety, tolerability, immunogenicity, and potential efficacy of RNA vaccine candidates against COVID-19 in healthy adults. Available at: http://clinicaltrials.gov/ct2/show/NCT04368728. Accessed June 2020.
  17. Pardi N, Hogan MJ, Porter FW et al. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov2018; 17 (4): 261–279.
  18. Merriam-Webster. Definition of plasmid. Available at: https://www.merriam-webster.com/dictionary/plasmids. Accessed June 2020.
  19. World Health Organization. DNA vaccines. Available at: https://www.who.int/biologicals/areas/vaccines/dna/en/. Accessed June 2020.
  20. gov. Safety, tolerability and immunogenicity of INO-4800 for COVID-19 in healthy volunteers. Available at: http://clinicaltrials.gov/ct2/show/NCT04336410. Accessed June2020.