The Impact of Advanced Age on Vaccine-Induced Tissue Immune Recall Responses

Abstract Infectious diseases account for one-third of deaths in individuals over the age of 65. Vaccines are a primary tool to combat infection, yet they are less effective in the aged population. Many have focused on vaccine-induced peripheral blood responses in old age; however, work from our lab demonstrates that immune responses to vaccination and infection in the periphery and local infection site (tissue) differ. To improve health outcomes in our aged population, we must study both systemic and tissue vaccine responses. We do so using a model of Mycobacterium bovis BCG vaccination and subsequent tuberculin skin test (TST) eight weeks after vaccination in adult and aged 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 responses in 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 immune proteins in aged baboon skin at the site of TST challenge, despite no alterations in antigen-specific peripheral blood mononuclear cell (PBMC) responses between age groups. Interestingly, cell migration assays show increased migration of PBMCs from aged BCG-vaccinated baboons, reinforcing the notion that systemic responses are not altered and that study of the tissue environment is important to understand responses to antigenic challenge with older age.