Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not older adults (VAC2P.936)

Although influenza vaccination is recommend for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing antibody titers, is increased in the elderly compared to young adults. The T follicular helper subset of CD4+ T cells provide B cell help in germinal centers and are necessary for class-switched antibody responses. Previous studies suggested a role for circulating T follicular helper cells (cTfh) following influenza vaccination in adults, but cTfh have not been studied in elderly adults where weak vaccine responses are often observed. Here, we studied cTfh expressing CXCR5 and Programmed Death 1 (PD-1). cTfh from elderly adults were present at reduced frequency, had decreased in vitro B cell help ability, and greater expression of activation marker inducible costimulator (ICOS) compared to young adults. At seven days after inactivated influenza vaccination, cTfh correlated with influenza vaccine-specific IgM and IgG responses in young adults but not in elderly adults. In sum, we have identified aging-related changes in cTfh which manifested as reduced influenza vaccine responses. Future rational vaccine design efforts should incorporate Tfh measurement as an immune correlate of protection, particularly in the setting of aging.