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.
Journal article
Wiley
2025-01-01T00:00:00+00:00
55