The Race for a COVID-19 Vaccine

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Written By Student Content

By Mariah Landry, RN, BSN, CCRN.  Ms. Landry is currently a student in Emory University’s Master of Science in Public Health program in Atlanta, Georgia, USA.  She earned her Bachelor of Science in Nursing at the University of Miami in Florida, USA, and she has since worked in both critical care and surgical nursing. 

The exhausting combination of discouraging PPE forecasts, complex preparedness measures, and increased global morbidity, beg the question of vaccination against SARS-CoV-2. Traditionally, vaccine development is not a speedy pursuit: on average, the process takes 15-20 years [1]. Vaccine development is segmented into pre-clinical testing and a four-phase clinical trial process. To accelerate the process, SARS-CoV-2 vaccines under trial are either truncating or bypassing the animal-model testing that usually comprises the bulk of pre-clinical experiments. Several regulatory agencies, including the U.S. Food and Drug Administration, have relaxed requirements for pre-clinical testing, helping researchers fast-track their work.

After the pre-clinical phase, a potential vaccine must pass through three phases of clinical trials prior to public distribution, and then a fourth phase after distribution [2]. Though countries vary in precise regulations, the World Health Organization has established a registry of trials worldwide and provides international standards for each phase.   The four phases of biomedical clinical trials are:

  • Phase I: Evaluates safe dosage range and identifies side effects of proposed drugs

  • Phase II: Tests drugs deemed safe in Phase II in a larger group to monitor for adverse effects

  • Phase III: Tests drugs on a larger population to establish efficacy, often pursued as a clinical trial

  • Phase IV: After country approval and distribution, evaluates effects of drug in a wide population over the long term

The majority of existing vaccines for viruses other than SARS-CoV-2 can be placed into any of four classical categories that each have risks and benefits [3]:

  • Inactivated viral vaccines: Stimulates immune response to antigens present on inactivated virus

    • Pros:

      • Can be used in immune-compromised populations

    • Cons:

      • Require adjuvants to activate immune system

      • Do not induce as strong or long-lasting an immune response as attenuated vaccines

  • Attenuated viral vaccines: Stimulate immune response similar to the natural infection

    • Pros:

      • Create long-lasting immune response

    • Cons:

      • Must be kept refrigerated

      • Can sometimes cause disease in immune-compromised populations

  • Subunit and acellular vaccines: Mimic antigens to stimulate immune response

    • Pros:

      • Induce a very specific and very strong immune response

      • Can be used in immune-compromised populations

    • Cons:

      • May require booster shots for long-term protection 

  • Toxoid vaccines: Target specific toxin produced by a germ

    • Pros:

      • Can work for bacterial diseases

    • Cons:

      • May require booster shots for long term protection

Vaccines targeting SARS-CoV-2 are also being developed using next generation platforms.  These platforms, outlined below, are advantageous as they can be developed based on sequence information alone [3].

  • Viral vector vaccines: Use a recombinant virus to deliver genes encoding target viral antigens

    • Pros:

      • Vectors can reduce pathogenicity

      • Stimulate strong humoral and cellular immune responses

    • Cons:

      • Theoretical risk from vector

  • Nucleic acid-based vaccines: Consist of DNA or mRNA that encode target viral antigens

    • Pros:

      • Can be adapted quickly to new viruses

      • mRNA vaccines may produce immunity at lower doses

    • Cons:

      • May require multiple doses for strong immune response

      • mRNA vaccines require carrier molecules to enable entry

  • Antigen presenting cells: Load this normal component of an immune response with peptides that would normally be produced in response to vaccination

    • Pros:

      • An individual’s cells can be harvested, manipulated, and infused back into the same individual

    • Cons:

      • Currently cost-prohibitive and time consuming

SARS-CoV-2 vaccine development is evolving rapidly.  According to the live Coronavirus Vaccine Tracker from the New York Times, there were 37 active clinical trials for putative vaccines by September 8, 2020.  of the end of September 8, 2020.  Ironically, clinical trials must be performed in areas where there is significant active community transmission of COVID-19 to determine efficacy of a SARS-CoV-2 vaccine.

There are currently three vaccines approved for limited use.  The Chinese government has approved a viral vector (adenovirus) vaccine developed by CanSinoBio for limited military use, though phase III trials are still underway in Saudi Arabia [4]. An inactivated vaccine developed by the Chinese company Sinovac has also been approved for emergency use, though phase III trials are still underway in Brazil and Indonesia.   Finally, on August 11, 2020, the President Vladimir Putin of Russia approved a viral vector (adenovirus) vaccine created by Gamaleya Research Institute before phase II trials had even begun, though this was later reduced to a conditional approval pending positive results from phase III trials.  Phase I/II results were published in The Lancet on September 4, 2020 [5].

Additional vaccine studies in phase III include: 

Progress in vaccine trials are an encouraging testament to human ingenuity. Nevertheless, political leaders and individuals alike should not let that detract from the continued importance of infection prevention.  Using South African outbreak data, scientists used a mathematical model to assess the ability of a future vaccine to contain the reproductive number COVID-19 in South Africa specifically. They found that a moderately effective vaccine would need to reach 94% coverage to reduce spread of the disease as effectively as stringent social distancing [6].  Although social distancing is difficult to maintain long-term, particularly in Africa, it will likely remain essential to reducing infection spread until a highly efficient or widely distributed vaccine is available. Even if multiple vaccines successfully complete phase III, supply chain issues will likely cause issues in international distribution.  The supply and demand economics at play for the prospective vaccine are of unprecedented scale and political complexity, and only time will tell what lies ahead for this global pandemic.

Ms. Landry has no financial involvement or interest in the Bio Africa Marketplace or products mentioned therein or elsewhere within the BioAfrica Innovation Hub websites. Her role in the Scientific Resource Hub does not constitute endorsement or recommendation of specific products or suppliers mentioned within the Bio Africa Innovation Hub websites.

 References

Publicly available websites and news articles are linked in the text. All images used were made freely available for use by Pixabay.

Full references for peer-reviewed articles or other sites not publicly accessible are available below. 

1.         Deb, B., H. Shah, and S. Goel, Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials. J Biosci, 2020. 45.

2.         Singh, K. and S. Mehta, The clinical development process for a novel preventive vaccine: An overview. J Postgrad Med, 2016. 62(1): p. 4-11.

3.         van Riel, D. and E. de Wit, Next-generation vaccine platforms for COVID-19. Nat Mater, 2020. 19(8): p. 810-812.

4.         Cyranoski, D., China's coronavirus vaccines are leaping ahead - but face challenges as virus wanes. Nature, 2020. 584(7819): p. 17-18.

5.         Logunov, D.Y., et al., Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. The Lancet.

6.         Mukandavire, Z., et al., Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios. PLoS One, 2020. 15(7): p. e0236003.

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