510. Secretory IgA in the Vaginal Mucosa Inhibits Herpes Simplex Virus Infection. (15th December 2022)

• Record Type: Journal Article
• Authors: Fong, Valerie; Hunte, Richard; Keller, Marla J; Herold, Betsy; Herold, Betsy
• Is Part Of: Open forum infectious diseases. Volume 9:(2022)Supplement 2
• Publication Date: 2022-12-15
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac492.566
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: HSV2 increases HIV risk and is twice as common among women. We previously showed that cervicovaginal secretions exhibit innate anti-HSV2 activity that was lower in adolescents and women with HIV-- conditions associated with vaginal dysbiosis and increased HSV shedding. Our current study aims to test the hypothesis that vaginal dysbiosis is associated with low anti-HSV activity and to explore the molecules and mechanisms that contribute. Methods: Cervicovaginal lavage (CVL) (10 ml normal saline wash) was collected from 20 women who presented with clinical bacterial vaginosis (BV) (Day 0) and then 1 and 4 weeks after completing a 7-day oral metronidazole course; parent study results were reported (PMID 34003290). Anti-HSV2 activity of CVL (diluted 1:4) was determined by plaque reduction assay. CVL IgG, IgA, cytokines and antimicrobial peptides were quantified by ELISA or multiplex Luminex and select microbiota by quantitative real-time PCR. CVL was enriched for IgA and IgG using protein L (binds all Ig) and Protein G (binds only IgG). HSV-specific antibodies in CVL were assessed by ELISA. Statistical analyses including Spearman correlation coefficients (SCC) were performed with GraphPad Prism version 9.1.2 software. Results: Anti-HSV2 activity of CVL was highly variable at Day 0 (mean 18.6% SD 36.7) and trended to increase after treatment (mean 22.56% SD 33.8). The anti-HSV2 activity correlated positively with Nugent scores (SCC= -0.28, p= 0.03) and qPCR levels of BV-associated microbes (SCC = -0.2 to -0.3, p< -0.1) but positively with IgA (r= 0.49, p< 0.01) and IgG (r= 0.33, p= 0.01). IgA and IgG were isolated from pools of CVL with high inhibitory activity greater than 40% (n= 8). The anti-HSV2 activity mapped to the IgA fraction (56.5% inhibition) compared to the IgG or non-Ig fraction (0% inhibition) even though, as expected, the CVL concentration of IgG was higher than IgA (8.3μg/mL vs 4.9 μg/mL). The anti-HSV2 activity did not correlate with HSV-specific Ig in CVL. Conclusion: Our findings suggest that secretory vaginal IgA contributes to innate anti-HSV2 activity and may trap viral particles to prevent viral entry. We speculate that sialidases, which cleave IgA and are elaborated by BV-associated microbiota, contribute to the low anti-HSV2 activity observed in high-risk cohorts. Disclosures: Betsy Herold, MD, Viracor (Eurofins): Advisor/Consultant|X-Vax, Technologies: Advisor/Consultant|X-Vax, Technologies: Grant/Research Support|X-Vax, Technologies: Serve on Scientific Advisory Board for X-Vax, Technologies and receiving reserach funding for related worl. Betsy Herold, MD, Viracor (Eurofins): Advisor/Consultant|X-Vax, Technologies: Advisor/Consultant|X-Vax, Technologies: Grant/Research Support|X-Vax, Technologies: Serve on Scientific Advisory Board for X-Vax, Technologies and receiving reserach funding for related worl.