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P3.363 Inflammatory Soluble Immune Mediators and Pathogenic Vaginal Bacteria Impact E. Coli Bactericidal Activity in Female Genital Tract Secretions
  1. R Pellett Madan1,
  2. C S Dezzutti2,3,
  3. L Rabe2,3,
  4. S L Hillier2,3,
  5. J Marrazzo4,
  6. I McGowan2,3,
  7. B A Richardson4,5,
  8. B C Herold1 Microbicide Trials Network Biomedical Sciences Working Group, 004MTN Protocol Team
  1. 1Albert Einstein College of Medicine, Bronx, NY, United States
  2. 2University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
  3. 3Magee-Womens Research Institute, Pittsburgh, PA, United States
  4. 4University of Washington, Seattle, WA, United States
  5. 5Fred Hutchinson Cancer Research Center, Seattle, WA, United States

Abstract

Background In low-risk women, in vitro inhibition of E. coli by genital tract secretions is associated with Lactobacillus crispatus and jensenii proteins. However in at-risk populations, HIV seroconversion was associated with greater E. coli bactericidal activity and inflammatory immune mediators. We therefore analysed the relationship between inflammation, E. coli bactericidal activity, and microbiota in vaginal swabs from participants in a safety study of VivaGel®.

Methods Swabs were collected before and after product use from subjects randomised to vaginal VivaGel® (n = 66), VivaGel® placebo (n = 65), or hydroxyethylcellulose (HEC) placebo (n = 54). Cytokines were quantified by multiplex proteome array and lactoferrin and SLPI by ELISA to generate a cumulative inflammatory score using principal components analysis. E. coli bactericidal activity in swab supernatants was quantified by a colony reduction assay. Vaginal bacteria were characterised by quantitative cultures. Generalized estimating equations controlling for product use were used for analyses.

Results Higher inflammatory score was associated with detection of Gardnerella vaginalis (OR 1.5; p = 0.02) and anaerobic gramme-negative rods (OR 1.4, p = 0.03), a trend towards diminished hydrogen peroxide-producing lactobacilli (OR 0.7, p = 0.1), and increased E. coli bactericidal activity (p < 0.001). The combined presence of group B streptococcus, E. coli, S. aureus, and enterococcus (potential pathogens) was associated with decreased E. coli bactericidal activity (p = 0.06). However these results were modified by gel type. Higher inflammatory score was associated with greater E. coli bactericidal activity only in the placebo arms (VivaGel® p < 0.001; HEC p = 0.002), while pathogenic bacteria were associated with decreased E. coli bactericidal activity in the VivaGel® arm (p = 0.001).

Conclusion Mucosal inflammation was associated with E. coli bactericidal activity in women using placebo gels, which could contribute to the previously observed link between bactericidal activity and HIV seroconversion. However bactericidal activity in women using VivaGel® was influenced by pathogenic bacterial populations, which may reflect an altered genital mucosal milieu.

  • E. coli
  • mucosal immunity
  • vaginal microbicide

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