Sex and age differences in B cell frequencies and antibody responses following influenza vaccination in highly vaccinated adult populations

Annual influenza vaccination is required for healthcare workers (HCWs, 18–49 years of age) at Johns Hopkins and is highly recommended to older adults (75+ years of age) to limit severe outcomes from annual influenza. As a result, vaccination rates and pre-vaccination immunity are high in both populations. We previously reported that sex differences in vaccine-induced antibody responses are not observed in these highly vaccinated populations, but that age-associated reductions in antiviral immunity following vaccination are more pronounced in males than females against both H1N1 and H3N2 viruses. Here, we conducted a clinical study of immune responses to the quadrivalent influenza vaccine to evaluate sex and age differences in influenza A vaccine (IAV) B cell including CD19+ B, plasmablasts (PB, CD3 −CD19 +CD38 ++CD71 +CD20 −IgD −H1 +H3 +), memory B cells (MB, CD3 −CD19 +CD71 −IgD −H1 +H3 +), and age-associated B cells (CD3 −CD19 +CD21 −CD11c −T-bet +H1 +H3 +) following receipt of the seasonal influenza vaccine in 2019–2020 and 2021–2022 seasons among male and female young adult HCWs and older adults. Both young and older females consistently have more total and IAV CD19+ B cells than males, with the greatest percentage being H1. Older adults, however, consistently have greater frequencies of IAV MB cells than young adults. Even with these cellular differences, males and females have equivalent post-vaccination neutralizing antibody titers against H1 and H3 influenza viruses. Whether the transcriptional profiles of B cells differ based on sex and age is currently under investigation. Taken together, these studies may provide mechanistic insights into variability in vaccine outcomes and protection based on the sex and age of the individual. U54AG062333