Approaches for creating a COVID-19 vaccine

Posted on March 16th, 2020 by Christy J. Wilson in Pharma R&D

Before the
coronavirus disease 2019 (COVID-19) pandemic, no one had ever heard of the
causative agent 2019 novel coronavirus (SARS-Cov-2). There were no approved antivirals
or vaccines for this virus or for any related coronaviruses (e.g., severe acute
respiratory syndrome–associated coronavirus (SARS-CoV) or Middle East
respiratory syndrome coronavirus).

Problems with COVID-19 vaccine development

Developing vaccines from scratch—which is required for COVID-19—is typically not a good option for stopping an ongoing pandemic. The extensive time required to develop a safe and effective vaccine that can prevent future disease in vaccine recipients (average of approximately 10 years) [1] means that the public health threat will end long before a candidate vaccine is licensed.

Vaccine development requires extensive planning regarding vaccine design, vaccine production and purification, preclinical testing in animals (to ensure some safety in humans), and multiple phases of clinical trials in humans (phase 1 for safety and phases 2 and 3 for efficacy). Companies taking the risk and proceeding with vaccine development for SARS-CoV-2 (at least 13 companies as of March 7, 2020) [2] are banking on the virus continuously circulating, so they have a population to conduct phase 2 and 3 trials with. If the virus disappears from circulation in China—or the perceived risk the virus poses to human health substantially declines—before phase 2 trials end, vaccine development will probably end.

Vaccine design approaches

Vaccines that
are safe and stimulate the right immune responses that confer protection from
disease are challenging to design. There are a number of different strategies companies
have used: live attenuated or inactivated viruses, virus-like particles or other
protein-based approaches, viral vector–­based vaccines or nucleic acid–based vaccines.
Of the potential SARS-CoV-2 vaccines in the pipeline, four involve
nonreplicating viruses or protein constructs, four have nucleic acid–based
designs, two contain live attenuated viruses and one involves a viral vector [2].
Regarding the previous SARS pandemic, one inactivated SARS-CoV [3] and one
DNA-based vaccine [4] made it through phase 1 trials before vaccine development
ended.

The
different approaches for vaccine design all carry different advantages and
disadvantages [5]. Approaches involving replicating viruses stimulate robust
immune responses, but safety is often a concern. Protein vaccines and nucleic
acid–based vaccines are often safer but typically have less immunogenicity, and
they require adjustments to induce stronger immune responses. Nucleic acid–based
vaccines are typically the fastest to get into phase 1 studies, but no nucleic
acid vaccine has been licensed for use in humans as of yet.

Because of
safety concerns involving older populations (who have higher risk for severe
disease), using a live attenuated virus might not be the best approach [6].
Patients with severe disease typically have T-helper 2 responses (immune
responses typically induced against extracellular parasites), so vaccines known
to elicit this type of immune response (inactivated viruses, virus vectors)
might also be best avoided. Vaccines involving protein-based (virus protein subunits,
virus-like particles, nanoparticles) or nucleic acid–based (DNA or RNA encoding
virus structural proteins) designs, which do not have known safety
disadvantages, might be the best approaches for SARS-CoV-2.

Unfortunately,
our knowledge of the immune response is not advanced enough for us to
accurately predict vaccine safety and efficacy. What we have to do (testing
multiple different strategies) is exactly what is being done. Only with results
from more extensive research will we know the absolute best approaches for
SARS-CoV-2 vaccine development. 

References

1. Pronker
   ES, Weenen TC, Commandeur H, Claassen EH, Osterhaus AD. Risk in vaccine
   research and development quantified. PLoS One. 2013;8(3):e57755. doi:
   10.1371/journal.pone.0057755.
2. Pang
   J, Want MX, Han Ang IY, et al. Potential rapid diagnostics, vaccine and
   therapeutics for 2019 novel coronavirus (2019-nCoV): a systematic review. J
   Clin Med 2020;9:623. doi:10.3390/jcm9030623.
3. Lin
   JT, Zhang JS, Su N, et al. Safety and immunogenicity from a phase I trial of
   inactivated severe acute respiratory syndrome coronavirus vaccine. Antivir
   Ther. 2007;12(7):1107-13.
4. Beigel
   JH, Voell J, Kumar P, et al. Safety and tolerability of a novel, polyclonal
   human anti-MERS coronavirus antibody produced from transchromosomic cattle: a
   phase 1 randomised, double-blind, single-dose-escalation study. Lancet Infect
   Dis. 2018;18(4):410-418. doi: 10.1016/S1473-3099(18)30002-1.
5. Rauch
   S, Jasny E, Schmidt KE, Petsch B.  New
   vaccine technologies to combat outbreak situations. Front Immunol 2018;9:1963.
   doi: 10.3389/fimmu.2018.01963.
6. Prompetchara
   E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines:
   Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020
   Feb 27. doi: 10.12932/AP-200220-0772.

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