ZMapp reduces diffusion of Ebola viral particles in fresh human cervicovaginal mucus

ABSTRACT

Vaginal transmission from semen of male Ebola virus (EBOV) survivors has been implicated as a potential origin of Ebola virus disease (EVD) outbreaks. While EBOV in semen must traverse cervicovaginal mucus (CVM) to reach target cells, the behaviour of EBOV in CVM is poorly understood. CVM contains substantial quantities of IgG, and arrays of IgG bound to a virion can develop multiple Fc-mucin bonds, immobilizing the IgG/virion complex in mucus. Here, we measured the real-time mobility of fluorescent Ebola virus-like-particles (VLP) in 50 CVM specimens from 17 women, with and without ZMapp, a cocktail of 3 monoclonal IgGs against EBOV. ZMapp-mediated effective trapping of Ebola VLPs in CVM from a subset of women across the menstrual cycle, primarily those with Lactobacillus crispatus dominant microbiota. Our work underscores the influence of the vaginal microbiome on IgG-mucin crosslinking against EBOV and identifies bottlenecks in the sexual transmission of EBOV.

KEYWORDS:

• Antibody
• Ebola
• mucosal barrier
• microbiome
• Immunoglobulin G (IgG)
• mucin

Disclosure statement

Intellectual property associated with harnessing antibody-mucin interactions described in part in this publication was developed at the University of North Carolina – Chapel Hill (UNC-CH), and has been licensed to Mucommune, LLC and Inhalon Biopharma. SKL is a founder of Mucommune and currently serves as its interim CEO, board of director, and scientific advisory board. SKL is also founder and Chief Scientific Officer of Inhalon Biopharma. SKL owns stock in both companies; SKL’s relationships with both companies are subject to certain restrictions under University policy and are managed by UNC-CH in accordance with its conflict-of-interest policies. JR is co-founder of LUCA Biologics, a biotechnology company focusing on translating microbiome research into live biotherapeutics drugs for women’s health.

Additional information

Funding

This work was supported by the National Institutes of Health (https://www.nih.gov/) grants including R21AI093242 (SKL), U19AI084044 (JR), and K23AI121516 (WAF), North Carolina Translational & Clinical Sciences Institute (NCTraCS) (NCATS; 1UL1TR001111 to WAF and SKL), and the David and Lucile Packard Foundation (https://www.packard.org/) 2013–39274 (S. K. L.). The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.