Vaginal microbicides are a female-controlled HIV prevention option whose early development faced challenges that necessitated the search for safety biomarkers in clinical trials. We started out with a group of 30 healthy Caucasian women in Antwerp, Belgium and characterized cellular and soluble immunity and the vaginal microbiome in the lower female genital tract. We also conducted both a cross-sectional and longitudinal characterization of the female genital tract in 430 sexually active women from Sub-Saharan Africa (Kenya, Rwanda and South Africa).

As generally expected, bacteria that are generally linked with good vaginal health, L. crispatus and L. vaginalis, were associated with lower levels of pro-inflammatory cytokines and higher levels of protective antimicrobial proteins. In contrast, BV-associated A. vaginae, G. vaginalis and P. bivia were associated with increased pro-inflammatory cytokines. Vaginal dysbiosis (specifically BV) was characterized by a clear pro-inflammatory signature and reduced levels of IP-10, SLPI and total protein.

Based on our findings, we propose pro-inflammatory IL-1 (α and β), IL-6, IL-8, IL-12(p70); anti-inflammatory IL-1RA; the chemokine IP-10; and the antimicrobial protein SLPI as a smaller panel of soluble biomarkers for consideration for safety measurement of candidate vaginal microbicides. Additionally, the assessment of microbicide safety should include clinical examination for visible signs of vaginal epithelia irritation and the effect of candidate microbicides on cellular markers of inflammation as well as the vaginal microbiome. An ideal outcome would be point-of-care tools that can be easily used in clinical setting in resource-limited settings to identify women with increased susceptibility to HIV infection.