A Vital Role for B Cells in Vaccine-Induced Pulmonary T Cell Immunity to Influenza Virus 9285

Abstract Description Current influenza vaccines primarily provide protection through subtype-specific antibodies targeting the mutation-prone surface proteins hemagglutinin and neuraminidase. However, these vaccines must be reformulated annually to match evolving seasonal strains. Broad immunity against heterosubtypic influenza A virus (IAV) infections, which could offer more durable protection, has been linked to tissue-resident memory (TRM) CD4 and CD8 T cells in mucosal sites. To address this, we developed a nano-emulsion-adjuvanted IAV nucleoprotein (NP)-based subunit vaccine that induces robust NP-specific CD4 and CD8 TRMs in the lungs and airways, providing broad protection against IAV strains. The cellular and molecular mechanisms driving the development and function of these vaccine-induced TRMs remain poorly understood. Our data show that depletion of B cells significantly reduced the activation and/or expansion of NP-specific CD4 T cells in the lymph nodes, spleen, lungs, and airways. In contrast, B cell depletion had a minimal effect on NP-specific CD8 T cell numbers in the MLNs and spleen, but impaired the trafficking and/or accumulation of effector CD8 T cells in the lungs and airways. These results suggest that B cells might play a critical role in supporting CD4 T cell activation and the trafficking of CD8 T cells to mucosal sites. Future studies will explore the complex interactions between B cells, CD4 T cells, and CD8 T cells in vaccine-induced mucosal immunity to IAV. Funding Sources National Institutes of Health (AI73757, AI124299) Topic Categories Vaccines and Immunotherapy (VAC)