COVID-19 Vaccine: The Path to Development

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, one question has frequently been on people’s lips: when will a vaccine be ready? Recently the head of the National Institute of Allergy and Infectious Diseases (NIAID), Anthony Fauci, MD, claimed that there will be 100 million doses of a coronavirus vaccine available by the year’s end.

However, the timing of availability of a vaccine against COVID-19 is unknown. The mumps vaccine has been considered the fastest developed vaccine to date, taking 4 years from virus sample to the vaccine being licensed in 1967.¹

What we do know is the process that any potential vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) needs to complete before being added to a Centers for Disease Control and Prevention (CDC) immunization schedule. Since January 2020, when China shared the whole genome sequence of the virus,² researchers have been working tirelessly to create a potential vaccine.

As of June 9, 2020, more than 100 vaccines are being investigated,³ and each one will be subject to the same approval process. A sponsor must first submit an Investigational New Drug application (IND) to the US Food and Drug Administration (FDA). Once the IND has been approved, companies can begin clinical trials in human volunteers.⁴ Trials occur in 3 phases; the first would have fewer than 100 volunteers, the second several hundred, and the third tens of thousands.

The trials will assess safety and efficacy to ensure that the vaccine is effective at preventing disease and that the benefits of the vaccine outweigh any presumed risks.  Once a license is granted, the FDA continues to monitor production of the vaccine through facility inspections. The FDA also continues to monitor reports of adverse events among the public.

Relatively recent advances in technology have made messenger RNA (mRNA) a viable therapeutic approach for conferring immunogenicity.⁵ So far, mRNA vaccines are the furthest advanced in COVID-19 vaccine development. One mRNA vaccine being developed in collaboration between the NIAID and Moderna, Inc., is now in phase 2, with phase 3 expected to begin in July.⁶ Pfizer Inc. and BioNTech are also jointly working on an mRNA vaccine and have initiated a phase 1/2 trial.

Once a vaccine is determined to be safe and effective, the challenge then becomes one of scale. How do you manufacture enough vaccines for such unprecedented times, when there is global demand for a product? A prospective manufacturer will need to scale up production without affecting the supply of other vital vaccines.  However, according to Chief Medical Officer, Tal Zaks, MD, PhD, Moderna is already addressing this need.  In an interview with NPR in March, Dr Zaks stated, “We’ve already begun the scale-up activity in our manufacturing site to be able to scale up and produce the vaccine that is going to be required.”

Once the FDA licenses a vaccine, the Advisory Council on Immunization Practices (ACIP) convenes to review all data regarding the vaccine. For a vaccine to be added to the recommended immunization schedule, the recommendation of the ACIP must be approved by the CDC.⁵

The level of effort and collaboration shown thus far has been commendable, and if in 18 months it results in a vaccine that protects against SARS-CoV-19, it would be unprecedented.

References

1. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 2015. Accessed June 10, 2020. https://www.cdc.gov/vaccines/pubs/pinkbook/mumps.html#vaccines

2. World Health Organization. Novel coronavirus – China. January 12, 2020. Accessed June 10, 2020. https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/

3. World Health Organization. Draft landscape of COVID-19 candidate vaccines. June 9, 2020. Accessed June 10, 2020. https://www.who.int/publications/m/item/draft-landscape-of-Covid-19-candidate-vaccines

4. Centers for Disease Control and Prevention. The journey of your child’s vaccine. July 30, 2018. Accessed June 10, 2020. https://www.cdc.gov/vaccines/parents/infographics/journey-of-child-vaccine.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fvaccines%2Fparents%2Finfographics%2Fjourney-of-child-vaccine-text.html

5. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261-279. doi: 10.1038/nrd.2017.243

6. Moderna. Moderna announces first participants in each age cohort dosed in phase 2 study of mRNA vaccine (mRNA-1273) against novel coronavirus. May 29, 2020. Accessed June 10, 2020. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-first-participants-each-age-cohort-dosed-phase