The role of old age on <i>Mycobacterium bovis</i> BCG vaccine-induced tissue immunity

Abstract Infections account for one-third of deaths in elderly individuals. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab demonstrates that immune responses to vaccination and infectious challenge differ between tissue sites and the periphery. To improve health outcomes in our aged population, we must study vaccine-responses in both the periphery and the local infection site (the tissue). We study this through a delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and subsequent tuberculin skin test (TST) eight weeks after vaccination in adult and elderly baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon TST challenge which we can study in skin biopsies reflecting tissue specific responses. Three days or one week after TST we examine BCG-specific memory responses in the skin biopsies. We also determine BCG-induced responses in the blood to compare tissue and systemic responses. We find increased oxidation and decreased production of cytokines, chemokines and growth factors in aged baboon skin at the site of TST challenge, despite no alteration in vaccine-induced peripheral blood responses between age groups. Based on these findings, we anticipate that alterations in the skin of aged BCG-vaccinated baboons will hinder T cell migration to and function in the tissue, thus decreasing vaccine-induced tissue immunity.