2024/11/27 by Lyn Yong, Claire Hutchings, Eleanor Barnes +2 · 1 voice
Immunology and Microbiology · Medicine · #Immunotherapy and Immune Responses #SARS-CoV-2 and COVID-19 Research #CAR-T cell therapy research
paper · pdf · doi:10.1002/eji.202451142
openalex publication_date 2024/11/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
ABSTRACT CD4 + T cells have been established as central orchestrators of cellular and humoral immune responses to infection or vaccination. However, the need for CD4 + T cell help to generate primary CD8 + T cell responses is variable depending on the infectious agent or vaccine and yet consistently required for the recall of CD8 + T cell memory responses or antibody responses. Given the deployment of new vaccine platforms such as nucleoside‐modified mRNA vaccines, we sought to elucidate the requirement for CD4 + T cell help in the induction of cellular and antibody responses to mRNA and adenovirus (Ad)‐vectored vaccines against SARS‐CoV‐2. Using antibody‐mediated depletion of CD4 + T cells in a mouse immunization model, we observed that CD4 + T cell help was dispensable for both primary and secondary CD8 + T cell responses to the BNT162b2 and mRNA‐1273 mRNA vaccines but required for the AZD1222 Ad‐vectored vaccine. Nonetheless, CD4 + T cell help was needed by both mRNA and Ad‐vectored vaccine platforms for the generation of antibodies, demonstrating the centrality of CD4 + T cells in vaccine‐induced protective immunity against SARS‐CoV‐2. Ultimately, this highlights the shared and distinct regulation of humoral and cellular responses induced by these vaccine platforms.