Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women

Introduction Innate activity against Escherichia coli in female genital secretions may represent contributions from vaginal bacteria and host soluble immune mediators. We analyzed the relationship between E. coli inhibitory activity, soluble immune mediators, and vaginal bacteria in participants in MTN-004, a placebo-controlled trial of VivaGel (R), a candidate product for topical HIV pre-exposure prophylaxis. Methods Escherichia coli inhibitory activity was quantified by colony reduction assay. Endocervical concentrations of interleukin (IL)-1 beta, IL-6, IL-12p40, macrophage inflammatory protein (MIP)-1 alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), lactoferrin, and secretory leukocyte protease inhibitor (SLPI) were quantified to generate a cumulative mediator score. Vaginal bacteria were characterized by quantitative cultures. Results In the two placebo arms, higher soluble immune mediator score was associated with greater E. coli inhibitory activity (beta = 17.49, 95% CI [12.77, 22.21] and beta = 13.28, 95% CI [4.76, 21.80]). However, in the VivaGel arm, higher concentrations of E. coli (beta = -3.80, 95% CI [-6.36, -1.25]) and group B Streptococcus (beta = -3.91, 95% CI [-6.21, -1.60]) were associated with reduced E. coli inhibitory activity. Conclusions Both host mediators and vaginal bacteria impact E. coli inhibition in genital secretions. The relative contributions of host mediators and bacteria varied between women who used VivaGel vs placebos.