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Respiratory syncytial virus (RSV) is a leading cause of serious lower respiratory tract disease in young children and older adults throughout the world. Prevention of severe RSV disease through active immunization is optimal but no RSV vaccine has been licensed so far. Immune mechanisms of protection against RSV infection in humans have not been fully established, thus a comprehensive characterization of virus-specific immune responses in a relevant animal model will be beneficial in defining correlates of protection. In this study, we infected juvenile naive AGMs with RSV A2 strain and longitudinally assessed virus-specific humoral and cellular immune responses in both peripheral blood and the respiratory tract. RSV viral loads at nasopharyngeal surfaces and in the lung peaked at around day 5 following infection, and then largely resolved by day 10. Low levels of neutralizing antibody titers were detected in serum, with similar kinetics as RSV fusion (F) protein-binding IgG antibodies. RSV infection induced CD8+, but very little CD4+, T lymphocyte responses in peripheral blood. Virus-specific CD8+ T cell frequencies were ~10 fold higher in bronchoaveolar lavage (BAL) compared to peripheral blood and exhibited effector memory (CD95+CD28-) / tissue resident memory (CD69+CD103+) T (TRM) cell phenotypes. The kinetics of virus-specific CD8+ T cells emerging in peripheral blood and BAL correlated with declining viral titers, suggesting that virus-specific cellular responses contribute to the clearance of RSV infection. RSV-experienced AGMs were protected from subsequent exposure to RSV infection. Additional studies are underway to understand protective correlates in these seropositive monkeys.

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Aging is met with multifaceted shifts in the makeup and function of immune cell populations, collectively known as “immunosenescence”, which render elderly populations more susceptible to pathogenesis of infectious disease and negatively impact responsiveness to vaccines. Highly efficacious vaccines to protect the elderly remain an unmet medical need. However, it has been demonstrated in recent years that robust vaccine responses can be generated in elderly populations through the use of adjuvants. While the positive impact of adjuvant inclusion in elderly vaccines is evident, a deeper understanding of the adjuvant-related, pathway-specific modulations necessary to overcome immunosenescence is needed. We hypothesize that by evaluating functional and phenotypic data from high-density immunoassays using aged murine and human samples we will identify mechanisms contributing to vaccine non-responsiveness in the elderly. To interrogate deficiencies in aged murine and human cytokine responses to immune pathway modulators, we utilized multiplex cytokine assays to compare young-versus-old in vitro cytokine expression of whole blood stimulated with TLR agonists. The results of these experiments will be discussed and could provide key insights for the rational use of adjuvants in vaccine development that may overcome age-related vaccine non-responsiveness and will also help bridge the gap in translatability of immune dysfunction-related findings between aged preclinical animal species and humans.