The overall goal of this proposal is to determine how vaccine type, sex, and gene expression influence both innate and T helper cell immune responses using systems biology and bioinformatics as tools to comprehensively assess the human transcriptome.

We will evaluate sex-dependent immune responses to two unique influenza vaccines in a population of older adults; the recently FDA-licensed MF59-adjuvanted influenza subunit vaccine (Fluad) and the high-dose split virion influenza virus vaccine (FluZone). The influence of sex on immune response to vaccination has been observed across multiple vaccines (including standard dose influenza vaccines, but the mechanisms are unknown, it affects all age groups regardless of hormonal status, and existing studies focus almost exclusively on humoral immune responses.

Relatively little is known about the effect of sex on innate and T helper responses following vaccination and we are unaware of any studies evaluating the effect of sex on immune responses to adjuvanted influenza vaccine.

The presence of adjuvant (MF59Flu) or higher antigen (Ag) dose leads to greater immunogenicity through mechanisms that have not been fully deciphered and are likely to be different. Further, a direct com-arison of innate and T helper immune responses between adjuvanted and high dose influenza vaccines has not been reported.