For vaginal transmission, viruses must penetrate mucus secretions to reach target cells;we recentiy found that Herpes Simplex Virus (HSV) and HIV readily diffuses through human cervicovaginal mucus. Most antibodies (Ab) produced by the immune system are secreted into mucus (not blood or lymph), and topical IgG provides robust protection against vaginal viral challenges. In addition to well-known antibody functions (e.g., neutralization, complement activation, opsonization), an important yet little recognized effector function of IgG is to trap viruses in mucus. IgG bound to a virus surface may form multiple low-affinity adhesive crosslinks between the virus and the mucus gel. A sufficient number of these low-affinity crosslinks, possibly at sub-neutralizing IgG concentrations, may permanently trap the virus in the mucus gel. Our pilot observations indicate that remarkably low concentrations of specific IgGI can trap HSV-1 and virus-like particles that otherwise rapidly penetrate mucus gels. Trapping reduces the flux of virus that reaches target cells, and facilitates inactivation and clearance by additional protective mechanisms. Trapping viruses in mucus before they can reach target cells is likely essential to protect against viruses that, once established, cause incurable infections. It is likely that the most protective antibodies will be those that not only neutralize virions by blocking viral entry into target cells, but also are highly effective at trapping virions in mucus. This potential IgG trapping function in mucus has been largely unrecognized because most studies of IgG activity have not been performed in mucus geis. Hence, all monoclonal antibodies (MAbs) developed to date has been developed without considering this immune function in mucus.

Public Health Relevance

Human immunodeficiency virus (HIV) and Herpes Simplex virus (HSV) both readily move through genital tract mucus secretions to transmit infections. Recent evidence suggests viral-specific antibodies in mucus may block viruses by trapping them in mucus. This project will aid in creating antibody-based vaginal microbicides designed to protect against HIV/AIDS and HSV/genital herpes.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-ESB-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
United States
Zip Code
Wang, Y-Y; Kannan, A; Nunn, K L et al. (2014) IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections. Mucosal Immunol 7:1036-44
Whaley, Kevin J; Morton, Josh; Hume, Steve et al. (2014) Emerging antibody-based products. Curr Top Microbiol Immunol 375:107-26
Anderson, Deborah J; Marathe, Jai; Pudney, Jeffrey (2014) The structure of the human vaginal stratum corneum and its role in immune defense. Am J Reprod Immunol 71:618-23
McKinley, Scott A; Chen, Alex; Shi, Feng et al. (2014) Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa. PLoS One 9:e100598
Chen, Alex; McKinley, Scott A; Wang, Simi et al. (2014) Transient antibody-mucin interactions produce a dynamic molecular shield against viral invasion. Biophys J 106:2028-36
Gunawardana, Manjula; Baum, Marc M; Smith, Thomas J et al. (2014) An intravaginal ring for the sustained delivery of antibodies. J Pharm Sci 103:3611-20
O'Hanlon, Deirdre E; Moench, Thomas R; Cone, Richard A (2013) Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One 8:e80074