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Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition

Mucosal Immunologyvolume 11pages14771486 (2018) | Download Citation



IgG possesses an important yet little recognized effector function in mucus. IgG bound to viral surface can immobilize otherwise readily diffusive viruses to the mucin matrix, excluding them from contacting target cells and facilitating their elimination by natural mucus clearance mechanisms. Cervicovaginal mucus (CVM) is populated by a microbial community, and its viscoelastic and barrier properties can vary substantially not only across the menstrual cycle, but also in women with distinct microbiota. How these variations impact the “muco-trapping” effector function of IgGs remains poorly understood. Here we obtained multiple fresh, undiluted CVM specimens (n = 82 unique specimens) from six women over time, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent Herpes Simplex Viruses (HSV-1) in CVM treated with different HSV-1-binding IgG. The IgG trapping potency was then correlated to the menstrual cycle, and the vaginal microbial composition was determined by 16 s rRNA. In the specimens studied, both polyclonal and monoclonal HSV-1-binding IgG appeared to consistently and effectively trap HSV-1 in CVM obtained at different times of the menstrual cycle and containing a diverse spectrum of commensals, including G. vaginalis-dominant microbiota. Our findings underscore the potential broad utility of this “muco-trapping” effector function of IgG to reinforce the vaginal mucosal defense, and motivates further investigation of passive immunization of the vagina as a strategy to protect against vaginally transmitted infections.

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This work was supported by the National Institutes of Health ( grants R21AI093242 (S.K.L.), U19AI096398 (S.K.L.), and U19AI084044 (J.R.), a Diversity Supplement 1F32AI102535 (K.L.N.), The David and Lucile Packard Foundation ( 2013-39274 (S.K.L.), the Eshelman Institute of Innovation (, S.K.L.), and startup funds from the University of North Carolina Eshelman School of Pharmacy (; S.K.L). The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.

Author information


  1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27519, USA

    • Holly A. Schroeder
    • , Kenetta L. Nunn
    • , Alison Schaefer
    • , Christine E. Henry
    • , Felix Lam
    •  & Samuel K. Lai
  2. UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27519, USA

    • Kenetta L. Nunn
    •  & Samuel K. Lai
  3. Mapp Biopharmaceutical Inc, San Diego, CA, 92121, USA

    • Michael H. Pauly
    • , Kevin J. Whaley
    •  & Larry Zeitlin
  4. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    • Mike S. Humphrys
    •  & Jacques Ravel
  5. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    • Jacques Ravel


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H.A.S., K.L.N., and S.K.L. conceptualized and designed the experiments; K.L.N. recruited study participants; H.A.S., K.L.N., C.E.H., F.L., M.S.H., and S.K.L. performed experiments; H.A.S., A.S., and S.K.L. performed data analysis; M.H.L., K.J.W., and L.Z. provided reagents; H.A.S. and S.K.L. wrote the paper; H.A.S., K.J.W., L.Z., J.R., and S.K.L. edited the paper.

Competing interests

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, L.LC. S.K.L. is a founder of Mucommune and currently serves as its interim CEO, board of director, and in the scientific advisory board. S.K.L. owns company stock; S.K.L.’s relationship with Mucommune is subject to certain restrictions under University policy. The terms of this arrangement are being managed by UNC-CH in accordance with its conflict of interest policies.

Corresponding author

Correspondence to Samuel K. Lai.

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