NONHUMAN PRIMATE MODEL OF IMMUNOSENESCENCE AND VACCINATION

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elderly people are at higher risk than young adults to suffering from morbidity and mortality associated with infectious diseases, and this is primarily due to the declining immune system, or immunosenescence, that occurs during aging. Immunosenescence also contributes to a decline in vaccine efficacy in the elderly, which poses a tremendous challenge to public health. The purpose of this study is to apply a nonhuman primate model of aging to test the hypothesis that older rhesus macaques ( 14 years of age) with lower levels of na[unreadable]ve T cells and function (ie. proliferation and turnover rates) will express lower immune responses to vaccination than age-matched older monkeys that have relatively higher levels of na[unreadable]ve T cells and function. The specific aims are: 1. Define baseline measures of immunosenescence among the older rhesus macaques at the Tulane National Primate Research Center (TNPRC). Levels of naive T cell populations (based on a series of CD surface markers) and proliferative / turnover (apoptosis) responses will be measured in approximately 150 older rhesus macaques ( 14 years old) at TNPRC. Additional characteristics that will be tested include rhesus macaque genotype (pedigree), social hierarchy, and presence of persistent herpes virus (eg. CMV) infections that are thought to drive immunological exhaustion and depletion of naive T cells. The combined results will be used to rank the older animals at TNPRC for selecting high and low "responders" for studies in aim 2. 2. Test the hypothesis that older NHPs with relatively lower populations of naive T cells and weaker immune function status (as defined in aim 1) will respond less favorably to secondary tetanus and primary influenza vaccinations than older age-matched NHPs with relatively higher levels of naive T cells and lymphocyte proliferative / apoptotic responses. Groups of older age-matched NHPs with high and low levels of na[unreadable]ve T cells and lymphocyte function (based on results of aim 1) will be administered tetanus boost (for testing 2[unreadable] responses) and influenza vaccinations (for testing 1[unreadable] responses). Changes in na[unreadable]ve T cell subpopulations and lymphocyte function (proliferation, apoptosis, and IFN-( expression via ELISA and ELISPOT), in response to mitogen (PHA) and vaccine antigen exposure ex vivo, will be measured to assess vaccination affects in older monkeys with relatively high versus low levels of na[unreadable]ve T cells and lymphocyte function. The relevance of these results is to support future research proposals to validate (prove) vaccine efficacy by challenging NHPs with the infectious agent after vaccination, a procedure that can not be applied experimentally to humans. Further relevance of this NHP model of aging is the potential to develop and apply immunological and social intervention strategies to rejuvenate the immune system in the elderly, and thereby improve vaccine efficacy.