T cells in SARS-CoV-2 infection and vaccination

Abstract

While antibodies garner the lion’s share of attention in SARS-CoV-2 immunity, cellular immunity (T cells) may be equally, if not more important, in controlling infection. Both CD8+ and CD4+ T cells are elicited earlier and are associated with milder disease, than antibodies, and T-cell activation appears to be necessary for control of infection. Variants of concern (VOCs) such as Omicron have escaped the neutralizing antibody responses after two mRNA vaccine doses, but T-cell immunity is largely intact. The breadth and patient-specific nature of the latter offers a formidable line of defense that can limit the severity of illness, and are likely to be responsible for most of the protection from natural infection or vaccination against VOCs which have evaded the antibody response. Comprehensive searches for T-cell epitopes, T-cell activation from infection and vaccination of specific patient groups, and elicitation of cellular immunity by various alternative vaccine modalities are here reviewed. Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed. While VOCs have not yet fully escaped T-cell immunity elicited by natural infection and vaccines, some early reports of partial escape suggest that future VOCs may achieve the dreaded result, dislodging a substantial proportion of cellular immunity, enough to cause a grave public health burden. A proactive, rather than reactive, solution which identifies and targets immutable sequences in SARS-CoV-2, not just those which are conserved, may be the only recourse humankind has to disarm these future VOCs before they disarm us.

Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study

“…Studies published between 2021 and 2022 showed high SARS-CoV-2-specific T-cell activation following severe disease 21 and impaired protection from infection in rhesus macaques ( Macaca mulatta ) following CD8 T-cell depletion, 22 suggesting that cellular immunity can contribute to protection against SARS-CoV-2. It was proposed that memory T cells might protect populations from severe infections, 23 , 24 perhaps when antibody titres are waning. In our study, only five participants with confirmed SARS-CoV-2 infection had severe disease and T-cell activation was measured in only one of these individuals, precluding analysis of a correlation between T-cell activation and severe disease.…”

Severe acute respiratory syndrome coronavirus 2 virus-like particles induce dendritic cell maturation and modulate T cell immunity

“…CD4 + T cells enhance the antibody and cytotoxic T lymphocyte responses. CD8 + T cells recognize virus-infected cells and eliminate them to limit viral spread ( Young, 2022 ). To precisely characterize the SARS-CoV-2 VLP activity on DC and T cell interactions, the syngeneic MLR assay was performed, which revealed that SARS-CoV-2 VLP treatment enhanced CD4 + and CD8 + T cell proliferation ( Figures 6A, B ).…”

“…In COVID-19, high T cell activity response is associated with milder disease, whereas a poor T cell response is associated with severe disease ( Young, 2022 ). In the present study, interestingly, the proliferation of both CD4 + and CD8 + T cells was negatively correlated with the concentration of VLPs.…”

Antibody Persistence After Primary SARS-CoV-2 Infection and Protection Against Future Variants Including Omicron in Adolescents: National, Prospective Cohort Study

“…Finally, we only assessed antibody titers and cross-reactivity after infection and vaccination. Protection against reinfection and, importantly, against serious disease will also depend T-cell responses, 35 which we did not assess in our cohort.…”