Age Impacts the Local Immune Response to Tuberculin Skin Challenge in Mycobacterium Bovis BCG-vaccinated Baboons

Abstract

Background - Individuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. 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 and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. To improve health outcomes in our aged population, we must study vaccine responses in the tissue. Here we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test (TST) in adult and aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short-term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In parallel, we determined BCG-induced responses in the peripheral blood of vaccinated animals. Results - In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. Phenotypic analysis of aged peripheral blood cells found several age-related changes in immune cell populations, independent of BCG vaccination, and no impairment in functional responses. Moreover, aged peripheral blood mononuclear cells had increased migration in vitro, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. Conclusions - These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.

Tuberculosis in an Aging World

“…Overall, chronic inflammation during aging hinders T-cell responses and interferes with vaccine efficacy [ 56 , 57 , 58 ]. For example, applying a delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test in old baboons showed impaired immune responses to antigenic challenges that varied between tissue sites and the periphery, limiting appropriate immune memory responses [ 59 ]. A follow-up study demonstrated a decrease or delay in T cell recall responses to the pulmonary challenge site in aged BCG vaccinated rhesus macaques [ 60 ].…”