Molecular signatures of aging and flu vaccine response in Healthy and HIV infected individuals

Individuals living with chronic HIV experience similar immune impairments as HIV-negative elderly however they manifest symptoms (e.g. suboptimal responses to vaccination) at a younger age. Mechanisms underlying premature immune-senescence are unclear. In this study, we aimed to identify molecular signatures of aging and vaccine response in HIV infected (HIV) individuals as compared to age-matched healthy-control participants (HC). Using RNA-sequencing, we evaluated transcriptomic profiles in peripheral blood mononuclear cells in study participants before and 1-week after influenza vaccination. Despite that fewer differentially expressed genes between young (<40yrs) and old (>59yrs) were observed in HIV, metabolic and innate immune activation pathways were associated with increasing age in both HIV and HC. Age was also associated with pathways involved with T cell immune activation in HC, and with Interferon signaling pathways in HIV. Predictive and correlative models of vaccine response using gene expression were different in HC and HIV. In this study, molecular signatures were defined for aging and vaccine response in HC and HIV. We observed signs of precocious immune aging at the transcriptional level in HIV and described a transcriptional perturbation associated with innate immunity and glucose metabolism induced by aging in both HC and HIV in resting conditions. Overall design: 48 individuals from the FLORAH cohort(13) were selected based on their HIV serostatus, age and response to influenza vaccination. 6 vaccine Responder and 6 vaccine Non-Responder were selected for each of the 4 groups in analysis, namely young HIV infected (YH), old HIV (OH), young healthy (YC) and old HC (OC). Samples were taken at pre-vaccination (T0) and 7 days post-vaccination (T1)