Effects of aging on vaccine efficacy in nonhuman primate models (104.1)

Abstract Vaccines are frequently less efficacious in the elderly and correlates of protection in older adults often differ from those seen in younger individuals. However, clinical testing of new vaccine formulations is typically limited and does not include elderly subjects. In order to identify a nonhuman primate (NHP) model that would recapitulate the effects of immunosenescence in humans, we assessed immune responses in three different NHPs: baboons (Papio), rhesus macaques (Macaca), and African green monkeys (Chlorocebus). The F1-antigen, a capsular protein encoded on the plague bacterium Y. pestis pFra plasmid, was chosen because it should elicit naive responses in all subjects. The animals were bled following primary and booster immunizations; B cell (antibody titer) and T cell parameters were assessed. As in humans, significant heterogeneity between individuals was seen. In rhesus and vervets, T cell responses to F1 were generally lower with increasing age. However, less of an age effect was observed in the baboons; this is consistent with the finding that antibody titers to F1 were not significantly diminished in older baboons and with our previous work showing immunization of old baboons with Y. pestis LcrV elicited high titer protective antibodies [JI 181:109]. Flow cytometric analyses of the T cell populations in old and young NHPs reveal differences across the species and provide additional insight into the immune parameters that correlate with healthy aging.