Sex differences in B cell dynamics after seasonal influenza vaccination are dependent on the age and hormonal status of vaccinees 3346

Abstract Description We evaluated sex differences and the effects of sex steroid hormones on the immune responses to the seasonal quadrivalent influenza vaccine (QIV) by analyzing influenza A virus (IAV)-specific B cell populations, single cell transcriptomics, and neutralizing antibody (nAb) responses among young adult (YA; 18-49 yo) healthcare workers at Johns Hopkins and older adults (OA; 75+ yo) in the Baltimore community, both of whom are highly vaccinated with pre-existing immunity. Prior to vaccination, CD19+ B cells from OAs, regardless of sex, showed evidence of inflammaging with greater enrichment of Hallmark pathways associated with inflammatory responses than YAs, including TNF activity. Among YAs, females had greater H3N2, but not H1N1, nAb titers, higher proportions of IAV-specific CD19+ B cells, and antibody secreting cells (ASCs) than males, which were not observed among OAs. scRNA-seq of CD19+ B cells revealed that YA females, compared to YA males, have greater transcriptional activity at 7 days post-vaccination, with upregulation of estrogen-responsive genes in the ASCs of females. In vitro treatment of PBMC samples from YAs and OAs with estradiol increased the number and size of HA-specific IgG+ ASCs for YA females, which were inhibited by the addition of tamoxifen prior to estradiol. Taken together, this study provides novel mechanistic insights into estradiol and its role in mediating the greater influenza vaccine-induced immunity among reproductive-aged females. Funding Sources Funding provided the National Institutes of Health NIA/ORWH Johns Hopkins Specialized Center of Research Excellence (U54AG062333) and the NIAID Johns Hopkins Center of Excellence for Influenza Research and Response (75N93021C00045). Topic Categories Computational and Systems Immunology (COMP)