SARS-CoV-2 vaccine(The Scientific and Technological Research Council of Turkey)

Vaccines effectively stimulate protective immune responses in healthy individuals, but the precise roles of germinal center (GC) and follicular helper T (TFH) cells in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine responses are not fully understood. This study used a conditional loss-of-function mouse model to investigate antibody responses to the Wuhan spike protein, specifically eliminating newly developed TFH cells during either the primary or memory phase. Our findings demonstrated that TFH-mediated GC responses are essential for primary vaccination. However, after booster immunization, memory B-cell responses were effectively regulated through extrafollicular mechanisms, independent of TFH cells. Ablating IL-4 receptor signaling in B cells attenuated antibody production in both the primary and memory phases, highlighting the critical role of IL-4 for optimal humoral immunity. We identified a unique population of IL-4-expressing memory T (IL-4+Tm) cells, characterized by CD27, GATA3, and IRF4 expression, that is strongly associated with these extrafollicular memory B-cell responses, capable of neutralizing SARS-CoV-2 variants. Furthermore, Omicron-based booster immunization recovered the immunity against emerging variants under TFH-deficient conditions. These results suggest that IL-4+Tm cells are an alternative pathway to sustain memory responses when GC function is impaired, particularly in immunocompromised states. Our study advances the understanding of memory T-cell-mediated humoral responses to SARS-CoV-2, offering insights for future vaccine strategies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in 2020 led to the immediate development of vaccines to combat SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19). First-generation (2020-2021) COVID-19 vaccines demonstrated high immunogenicity and efficacy, successfully reducing hospitalization, disease severity and COVID-19 related deaths. However, the initial clinical trials for these vaccines focused on overall healthy individuals, and generally excluded high risk populations, such as people with cancer. The SARS-CoV-2 VaccinE Response, Immunological eFfects and safetY in patients with Cancer (VERIFY-C) study formed a unique cohort in early 2021, to capture the initial immune response to BNT162b2 mRNA (Pfizer) vaccination in people with cancer, with or without ongoing/recent exposure to systemic cancer treatment. Fifty-three participants diagnosed with cancer were enrolled. Majority were non-Hispanic, Caucasian females. Patients under cancer treatment had significantly lower antibody responses than those without treatment at pre-second dose and 1-month post-second dose. The levels at 6-months post-second dose were similar between both groups. Patients under treatment had a significantly lower immune response 1-month post-second dose, with an increased immune response at 6-months post-second dose, suggesting a delayed immune response. Further investigations are needed to understand antibody functionality post-vaccination in these individuals.