The research article “T cell immunity to COVID-19 vaccines” highlights the importance of T cells in the immune response to COVID-19 vaccines. While most current research has focused on neutralizing antibodies (NAbs), recent findings highlight the important role of T cell responses in protecting against severe COVID-19, especially from variants that evade antibody recognition. These insights could guide improvements in current COVID-19 vaccines and influence the design of future vaccines for other diseases.
NAbs serve as the frontline defense by blocking the virus from entering cells in the upper respiratory tract, thereby reducing infection risk. However, NAb levels wane as time goes on, reducing their effectiveness in preventing infection (2). T cells, particularly CD4+ helper T cells and CD8+ cytotoxic T cells, act as an essential second line of defense. While T cells cannot prevent initial infection, they target and eliminate infected cells, controlling viral replication and reducing disease severity (1).
Memory T cells induced by COVID-19 vaccines remain effective over long periods, even as NAb levels decline (1). They recognize viral peptides in various protein regions, not limited to the frequently mutated spike protein region targeted by NAbs, making them less susceptible to variant escape. T cells’ response to peptides presented by host cells is highly specific and long lasting, providing protection that lasts months to years after vaccination.
T cells are crucial in preventing severe disease when NAbs fail to neutralize new variants like Omicron, which are better at evading antibody recognition. Studies in populations indicate that even with low or waning antibody levels, robust T cell responses correlate with a lower incidence of hospitalization and severe side effects (1).
With the rise of highly transmissible variants that evade NAbs, it has become clear that preventing infection entirely may be unrealistic with current vaccines. Instead, vaccines have shown effectiveness in limiting the severity of illness, largely due to the sustained activity of T cells. Variants like Omicron present mutations that can hinder NAb binding, yet more than 80% of T cell antigenic determinants remain conserved across these variants, maintaining T cell efficacy (1).
Future vaccines could benefit from targeting other viral proteins alongside the spike protein to broaden T cell immunity and create vaccines with broader protection against different coronavirus strains. Researchers are exploring updated booster formulations, but simply increasing NAb concentrations may not substantially enhance protection in the long term without understanding and optimizing T cell responses.
T cells are a critical component of durable immunity against infections and diseases like COVID-19. T cells, recognizing shorter viral peptide fragments, activate various antiviral actions. CD8+ T cells directly kill infected cells and produce antiviral signals, while CD4+ T cells activate B cells to produce an antiviral response (1). Antibodies produced by B cells follow a two-phase process: short-lived cells produce low-quality antibodies quickly, while long-lived plasma cells produce higher-quality antibodies after affinity maturation in germinal centers (1). Memory B cells, which store these high-quality antibodies, can rapidly respond upon reinfection, even as antibody levels naturally decline over time. This durable memory supports lasting protection, aided by T cell immunity.
- Wherry, E. J., & Barouch, D. H. (2022). T cell immunity to COVID-19 vaccines. Science. https://doi.org/10.1126/science.add2897
- Pegu, A., O’Connell, S. E., Schmidt, S. D., O’Dell, S., Talana, C. A., Lai, L., Albert, J., Anderson, E., Bennett, H., Corbett, K. S., Flach, B., Jackson, L., Leav, B., Ledgerwood, J. E., Luke, C. J., Makowski, M., Nason, M. C., Roberts, P. C., Roederer, M., Rebolledo, P. A., … Shi, P. Y. (2021). Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants. Science (New York, N.Y.), 373(6561), 1372–1377. https://doi.org/10.1126/science.abj4176