In Sub-Saharan Africa, young women 15–24 years of age account for nearly 30% of all new HIV infections, however, biological and epidemiological factors underlying this disproportionate infection rate are unclear. In this study, 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 = .02), and sCD40L trended higher (adj p = .06) in vaginal cytobrushes of adults. Proteomic analysis of vaginal biopsies showed no significant (adj p < .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 assessment and intervention strategies for epidemic control of this uniquely vulnerable population.

中文翻译：

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青少年与成年猪尾猕猴雌性生殖道中猿猴免疫缺陷病毒的易感性、免疫学和微生物组

在撒哈拉以南非洲地区，15-24 岁的年轻女性占所有新发艾滋病毒感染者的近 30%，然而，造成这种不成比例的感染率的生物学和流行病学因素尚不清楚。在这项研究中，我们使用青少年 ( n  = 9) 和成人 ( n = 9) 评估了女性生殖道 (FGT) 中 SIV/HIV 易感性的生物学因素。 = 10) 每周接受低剂量 SIV 阴道内攻击的猪尾猕猴 (PTM)。通过流式细胞术和细胞因子测定捕获 PTM 阴道组织中的免疫学变量。通过蛋白质组分析对阴道活检进行分析。通过 16S rRNA 测序评估阴道微生物组。我们有能力检测到不同年龄组之间的感染率增加了 2.2 倍，但我们发现易感性没有显着差异。该模型无法捕获流行病学因素，或者可能无法最好地代表 HIV 易感性的生物学差异。测量的免疫细胞亚群在各组之间没有显着差异。炎症标志物 MCP-1 显着升高 (adj p  = .02)，并且 sCD40L 呈升高趋势 (adj p = .06) 在成人阴道细胞刷中。阴道活检的蛋白质组学分析显示各组之间没有显着的 (adj p  < .05) 蛋白质或途径差异。各组之间的阴道微生物组没有显着差异。在该 PTM 模型中，各年龄组之间没有观察到差异，但是，这些动物可能无法反映导致 HIV 风险的生物因素，例如在人类同类中发现的生物因素。因此，该模型不适合探索人类青少年艾滋病毒风险的差异。年轻女性仍然是艾滋病毒感染的重点人群，仍需要对这一独特易感人群的疫情进行综合评估和干预策略。