How COVID-19 mRNA Vaccines Work

mRNA vaccines employ a novel strategy to stimulate immunity against coronavirus spike proteins

Amanda Maxwell, PhD

Initial reports of an atypical pneumonia-like respiratory infection started emerging from China in late December 2019, with sequencing data on the novel viral pathogen—SARS-CoV-2—available from January 11, 2020. Thailand reported the first case of COVID-19 outside of China on January 13, 2020, with a second report from Japan three days later. With increasing cases arising around the world and confirmed human-to-human infectivity, on March 11, 2020 the World Health Organization (WHO) classified the outbreak as a pandemic

Since then, more than 88 million cases have been recorded worldwide and more than 1.8 million people have died. In an effort to stop the spread, many countries now promote social distancing and wearing masks to reduce transmission while they wait for effective vaccines to become available.

A global pandemic places enormous pressure on vaccine research, production, and distribution. But now, only ten months after the WHO announced the pandemic, there are already vaccines available. Based on work from the previous SARS-CoV outbreak in 2003, researchers quickly identified ACE2, a cell-surface protein found in many different types of tissue, as a major host cell ‘receptor’ for SARS-CoV-2. Glycosylated spike (S) proteins on the outer surface of the virus bind ACE2. Disabling these spike proteins stops infection, making them ideal targets for a vaccination strategy. 

The two leading vaccine products, mRNA vaccines from Moderna and Pfizer/BioNTech, each features a novel strategy to stimulate immunity against these spike proteins. Already under investigation for treating individuals with HIV, Ebola, and Zika viral infections and certain cancers such as melanoma, these vaccines use synthetic mRNA engineered from the viral genetic material. Both vaccines contain single stranded (ss), nucleoside-modified viral mRNA that encodes the spike protein. They stimulate immunity by getting the host cell to create the spike protein antigen that primes the immune system, in contrast to traditional injections of inactivated virus or viral protein components. Since the vaccine mRNA encodes only the spike protein and not the whole virus, there is no danger of infection and it degrades inside the host cell within a few days.


References

Alberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Molecular Biology of the Cell. New York: Garland Science, 2002. Print.

Chung, Young Hun, et al. "COVID-19 vaccine frontrunners and their nanotechnology design." ACS Nano 14.10 (2020): 12522-12537.

DiPiazza, Anthony T., Barney S. Graham, and Tracy J. Ruckwardt. "T cell immunity to SARS-CoV-2 following natural infection and vaccination." Biochemical and Biophysical Research Communications (2020).

Hu, Ben, et al. "Characteristics of SARS-CoV-2 and COVID-19." Nature Reviews Microbiology (2020): 1-14.

Izda, Vladislav, Matlock A. Jeffries, and Amr H. Sawalha. "COVID-19: A review of therapeutic strategies and vaccine candidates." Clinical Immunology (2020): 108634.

Pardi, Norbert, et al. "mRNA vaccines—a new era in vaccinology." Nature Reviews Drug discovery 17.4 (2018): 261.

Wang, Fuzhou, Richard M. Kream, and George B. Stefano. "An evidence-based perspective on mRNA-SARS-CoV-2 vaccine development." Medical Science Monitor 26 (2020): e924700-1.


Amanda Maxwell, PhD

Amanda Maxwell is an established freelance science writer and communicator, who combines post?doctoral clinical research with non-profit experience to bring analytical skills and curiosity into her writing. Her work has appeared on Northrop Grumman's blog, NOW., Accelerating Science (Thermo Fisher Scientific), R.E.D. by Canadian Blood Services, and Simon Fraser University's Research Matters. She describes herself as a digital space explorer, engaging readers by translating complex theories and subjects creatively into everyday language.