Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine

Abstract

Efficacy of the immune response to vaccine depends on genetic background, sex and age of the recipient. However, mechanisms underlying this phenomenon have not been elucidated, yet. The study investigated influence of sex and age on serum IgG response to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6 mice, and mechanisms underlying this response. Total serum IgG responses to influenza virus type A strains declined with aging, in a strain-specific manner. Consequently, strain differences (greater IgG responses in BALB/c mice) observed in young mice (three-month-old) were abrogated in old (eighteen-month-old) ones. However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The strain/sex-specific differences in age-related changes in the magnitudes of IgG responses to TIV correlated with those in number of germinal centre (GC) B splenocytes. These differences were related to those in B splenocyte and CD4+ splenocyte proliferation in culture upon restimulation with influenza viruses from TIV. The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging, irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios (reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6 mice, respectively. Thus, although in young mice of both strains these ratios were comparable between sexes, in old females they were shifted towards IgG1 when compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios in splenocyte cultures stimulated with influenza viruses from old females of both strains were shifted towards IL-4 compared with that in age-matched male cultures. The study stimulates further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in elderly.