SIV susceptibility, immunology and microbiome in the female genital tract of adolescent versus adult pigtail macaques

In Sub-Saharan Africa, young women aged 15-24 account for nearly 30% of all new HIV infections, however biological and epidemiological factors underlying this disproportionate infection rate are unclear. Here, we assessed biological contributors of SIV/HIV susceptibility in the female genital tract (FGT) using adolescent (n=9) and adult (n=10) pigtail macaques (PTMs) with weekly low-dose intravaginal challenges of SIV. Immunological variables were captured in vaginal tissue of PTMs by flow cytometry and cytokine assays. Vaginal biopsies were profiled by proteomic analysis. The vaginal microbiome was assessed by 16S rRNA sequencing. We were powered to detect a 2.2-fold increase in infection rates between age groups, however we identified no significant differences in susceptibility. This model cannot capture epidemiological factors or may not best represent biological differences of HIV susceptibility. No immune cell subsets measured were significantly different between groups. Inflammatory marker MCP-1 was significantly higher (adj p=0.02), and sCD40L trended higher (adj p=0.06) in vaginal cytobrushes of adults. Proteomic analysis of vaginal biopsies showed no significant (adj p<0.05) protein or pathway differences between groups. Vaginal microbiomes were not significantly different between groups. No differences were observed between age groups in this PTM model, however these animals may not reflect biological factors contributing to HIV risk such as those found in their human counterparts. This model is therefore not appropriate to explore human adolescent differences in HIV risk. Young women remain a key population at risk for HIV infection, and there is still a need for comprehensive assessments and interventions strategies for epidemic control of this uniquely vulnerable population.