Change Is the Operative Word When Discussing COVID-19 Vaccines

As the global COVID-19 pandemic drags on, Americans are still arguing, debating, and discussing vaccinations.

This is a good time for pharmacists to review the general principles behind the COVID-19 vaccinations, extra doses, and booster shots, which are different things.

The Basics

All vaccines have identical goals.¹ First, they should protect against disease and/or infection caused by a pathogen during postvaccination exposure. Second, they should prevent infection transmission, a concept related to herd immunity. Live (attenuated) or nonlive (inactivated) vaccines and protein or polysaccharide antigen(s) have been successful for many years. In response to the pandemic’s dire consequences, pharmaceutical companies developed new vaccines based on nucleic acid (DNA and RNA) and viral vector technology.¹

After vaccination, 3 biologic activities occur first.1 Dendritic cells activate and present antigens. B cells produce antibodies, T cells work on cellular immunity and immune memory, and T helper cells relay signals that stimulate B cells and cytotoxic T cell production. Finally, cytotoxic T cells kill infected cells.¹

The most important step is B cell production of circulating antibodies because it drives sterilizing immunity, the situation in which the immune system stops a pathogen completely.^1,2 T cell response is an additional contributing factor. T helper cells can drive cellular immunity, B cell development and antibody production, and mucosal surface immunity. Finally, cytotoxic T cells seem to prevent progression to more severe disease.^1,3 Table 1^1,3 lists other factors that improve protection.

Other factors are vaccine specific. Virologists have examined various measures of efficacy for the COVID-19 vaccines. Although it would be ideal if the vaccines protected from any SARS-CoV-2 infection, it appears that the current vaccines protect from most infections, especially life-threatening and severe ones. Virologists also look at each pathogen’s incubation period and infection process.⁴ In addition, they examine circulating body concentrations and elimination half-life, with specific attention to whether the amount of antibody varies among individuals.1 Although it usually takes 3 to 4 days for individuals to develop some immune memory or reactivate antibody production, virologists look at each vaccine’s individual profile.¹

Next, virologists must look at the vaccine’s real-world performance so they can determine whether patients need booster shots or extra doses.⁵ The decision to recommend either is based on whether patients develop an adequate response to an initial vaccination series, associated with long incubation-period infections, or a less optimal response to an initial vaccination series, associated with short incubation-period infections.⁵

"Booster" Vs "Additional Doses"

Almost everybody who has been approved for a COVID-19 vaccine needs an additional dose or booster shot to maintain immunity.^1,5 Certain factors drive that need. The circulating SARS-CoV-2 viral variants are relatively resistant to antibody neutralizing activity.⁶ This means they have an efficient, fast infection process. Virologists have documented declining circulating antibody levels in individuals who have had an adequate response to primary vaccination but who have high-exposure risk, a high risk of severe disease, and/or a low initial response. Another contributing factor has been insufficient herd immunity.^1,6

Boosters are recommended when the response to the primary series of any vaccine is sufficient but immunity wanes over time.⁷

Virologists measure waning immunity via declining antibody titers in vaccinated individuals or epidemiologic evidence of increased infections or severe disease.⁷

Additional doses are recommended when the patient’s immunity is inadequate or the response to the originally designed primary series of the vaccine is insufficient.⁷ In the former case, epidemiologic evidence indicates that vulnerable populations have no or limited protection from infections or severe disease or that patients have low or unmeasurable antibody titers.

Table 2⁷ lists factors that influence response to the initial vaccine series.⁷

Immunizers should be aware of the CDC’s recommendations for additional doses of mRNA vaccines. As of January, the CDC recommends additional doses for moderately to severely immunocompromised people, meaning individuals who are actively taking high-dose corticosteroids or immunosuppressants, are receiving active cancer treatment, have advanced or untreated HIV infection, have a moderate to severe primary immunodeficiency, or received a stem cell transplant within 2 years or an organ transplant and are taking immunosuppressants.⁷

Conclusion

Patients who mount no detectable serum anti-body response to the COVID-19 vaccines still have an approximately 50% protection from infection compared with unvaccinated individuals.⁸ CDC recommendations change, and the astute immunizer should bookmark CDC pages and visit them often. Research is evolving continually, and the need for a booster shot does not mean these vaccines do not work; they work well.

Jeannette Y. Wick, MBA, RPh, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.

References

1. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021;21(2):83-100. doi:10.1038/s41577-020-00479-7

2. Rey GU. T cell responses to coronavirus infection are complicated. Virology blog. November 5, 2020. Accessed January 10, 2022. https://www.virology.ws/2020/11/05/t-cell-responses-to-coronavirus-infection-are-complicated/

3. Kourtis AP, Read JS, Jamieson DJ. Pregnancy and infection. N Engl J Med. 2014;370(23):2211-2218. doi:10.1056/NEJMra1213566

4. Kelly DF, Pollard AJ, Moxon ER. Immunological memory: the role of B cells in long-term protection against invasive bacterial pathogens. JAMA. 2005;294(23):3019-3023. doi:10.1001/ jama.294.23.3019

5. Mbaeyi S, Oliver SE, Collins JP, et al. The Advisory Committee on Immunization Practices’ interim recommendations for additional primary and booster doses of COVID-19 vaccines - United States, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(44):1545- 1552. doi:10.15585/mmwr.mm7044e2

6. Rodda LB, Netland J, Shehata L, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Cell. 2021;184(1):169-183.e17. doi:10.1016/j.cell.2020.11.029

7. Goswami ND. Clinical considerations for use of an additional mRNA COVID-19 vaccine dose after a primary mRNA COVID-19 vaccine series for immunocompromised people. CDC. August 13, 2021. Accessed January 10, 2022. https://www.cdc.gov/vaccines/ acip/meetings/downloads/slides-2021-08-13/03-COVID-Goswa- mi-508.pdf

8. GilbertPB,MontefioriDC,McDermottAB,etal.Immunecorrelates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science. 2022;375(6576):43-50. doi:10.1126/science.abm3425