CMV and inflammation contribute to decreased B cell vaccine response in the elderly (LYM6P.777)

Abstract

Abstract We previously showed intrinsic age-related defects in the in vivo and in vitro B cell responses to the seasonal influenza vaccine. Serum antibody responses were associated with the in vitro B cell response to the vaccine, measured by AID (activation-induced cytidine deaminase). Both responses decrease with age and are significantly correlated. In order to develop predictive markers for a beneficial humoral immune response, we measured markers of systemic and B cell-intrinsic inflammation. We hypothesized that the increased pro-inflammatory status of the elderly (including CMV) would directly impact B cell function, thus impairing the capacity of the individual to respond to vaccination. Our results show that aged B cells themselves make TNF-α before vaccine challenge, which positively correlates with serum markers of inflammation, but negatively correlates with B cell function, measured by AID expression after B cell stimulation. From the last 2 years (2011/2012 and 2012/2013) we show that CMV seropositivity is associated with lower in vivo and in vitro vaccine responses in both young and elderly. Recent studies will also be presented on the CD4 and CD8 TEMRA shown to be associated with lower antibody response. Our results reveal new molecular mechanisms which contribute to reduced antibody responses in aging and suggest that these will have an impact for crucial development of effective vaccines to protect the elderly from infectious and other debilitating diseases.