When the first Covid vaccines became available in the U.S., they ushered in a new era of hope that pandemic days might soon be over. And, indeed, the introduction of vaccines largely saw a decrease in mortality rates, complication rates, hospitalization rates, and eventually the de-escalation of lockdowns in areas of high compliance.1 Yet despite these positive changes, a large wave of infections in 2022 – driven by the Omicron variant of the virus – proved that some levels of immune protection provided by vaccines were susceptible to evasion through viral evolution. In other words, the versions of the Covid vaccine which are currently available to the public are no longer as effective for the most prevalent Covid variants. For at-risk populations in particular, this could mean increased risk of hospitalization and other Covid-related complications. If the world is to return to its pre-pandemic state, scientists and physicians alike are considering the need to update Covid vaccines for the future in order to protect the public against new Covid variants.
The practice of “updating” vaccines is not novel. Consider the influenza vaccine, of which a new version is released annually based on predictions of the most dangerous and pathogenic variants to circulate the following year. Since many people are already in the practice of receiving an annual flu vaccine, a hypothetical annual Covid vaccination would pose little disruption to the world of preventative medicine. In fact, the infrastructure and practices that already exist for flu vaccinations could be used synergistically to deliver such Covid vaccines. These plans are detailed in a paper published by FDA commissioner Dr. Robert Califf in early May of 2022:
“During the 2022-2023 COVID-19 vaccine planning and selection process, it is important to recognize that the fall season will present a major opportunity to improve COVID-19 vaccination coverage with the goal of minimizing future societal disruption and saving lives. With the plan for implementation of this year’s vaccine selection process, society is moving toward a new normal that may well include annual COVID-19 vaccination alongside seasonal influenza vaccination.”2
Yet it is important to note that there are key differences between the influenza vaccine and the Covid vaccine: the former typically uses inactivated virus or viral antigens,3 whereas the latter is delivered using mRNA-mediated technology. This can pose some challenges for the development of future updated Covid vaccines.
Covid variants which have been able to persist despite mass vaccination typically have alterations to their spike protein, which was the original target of the vaccine-induced immune response. Therefore, novel vaccine candidates tend to involve a change in target. Several avenues are being explored: for example, vaccines which target both the original form of Covid as well as components of the updated variants, or just the new variants entirely.4,5 Another possibility is the development of vaccines which target more stable components of the virus which are less likely to be able to change. Notably, predicting stability can be difficult, especially within the context of mass vaccination-induced selective pressure. An exciting paper recently published in the New England Journal of Medicine explored the possibility of employing Covid-neutralizing antibodies at its typical entry points: the nose and throat.4 The intended result would be a protective barrier which stops infection before it can even start.
Several of the vaccine-producing pharmaceutical giants are highly invested in the development of updated vaccines, with updated boosters from Moderna and Pfizer receiving emergency use authorization last week.5 Time will tell which versions are the most effective, and how updating Covid vaccines will continue to be done in the future.
References
1 Centers for Disease Control and Prevention. (n.d.). CDC Covid Data tracker. Centers for Disease Control and Prevention. Retrieved from https://covid.cdc.gov/covid-data-tracker/#vaccine-effectiveness
2 Marks, P., Woodcock, J., Califf, R. (2022, May 17). Covid-19 vaccination-becoming part of the new normal. JAMA. Retrieved from https://jamanetwork.com/journals/jama/article-abstract/2792030
3 Centers for Disease Control and Prevention. (2022, August 25). Seasonal flu vaccines. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/flu/prevent/flushot.htm
4 Planchais, C., Fernández, I., Bruel, T., de Melo, G. D., Prot, M., Beretta, M., Guardado-Calvo, P., Dufloo, J., Molinos-Albert, L. M., Backovic, M., Chiaravalli, J., Giraud, E., Vesin, B., Conquet, L., Grzelak, L., Planas, D., Staropoli, I., Guivel-Benhassine, F., Hieu, T., … Mouquet, H. (2022, July 4). Potent human broadly SARS-COV-2–neutralizing IGA and IGG antibodies effective against Omicron Ba.1 and BA.2. Journal of Experimental Medicine. Retrieved from https://rupress.org/jem/article/219/7/e20220638/213286/Potent-human-broadly-SARS-CoV-2-neutralizing-IgA
5 Coronavirus (COVID-19) Update: FDA Authorizes Moderna, Pfizer-BioNTech Bivalent COVID-19 Vaccines for Use as a Booster Dose. Food and Drug Administration. (2022, August 31). Retrieved from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-pfizer-biontech-bivalent-covid-19-vaccines-use
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