Vaginal Product Formulation Alters the Innate Antiviral Activity and Glycome of Cervicovaginal Fluids with Implications for Viral Susceptibility

Sujeethraj Koppolu, Linlin Wang, Ayushi Mathur, Jayeshwar A. Nigam, Charlene S. Dezzutti, Charles Isaacs, Leslie Meyn, Katherine E. Bunge, Bernard J. Moncla, Sharon L. Hillier, Lisa C. Rohan, Lara K. Mahal

Research output: Contribution to journalArticle

Abstract

Glycosylated proteins (i.e., mucins, IgG) are important mediators of innate antiviral immunity in the vagina; however, our current knowledge of the role that glycan themselves play in genital immunity is relatively low. Herein, we evaluate the relationship between innate antiviral immunity and glycomic composition in cervicovaginal lavage fluid (CVL) collected as part of a Phase I clinical trial testing the impact of two distinct formulations of the antiretroviral drug dapivirine. Using lectin microarray technology, we discovered that formulation (hydrogel- versus film-based delivery) impacted the CVL glycome, with hydrogel formulations inducing more changes, including a loss of high-mannose. The loss of this epitope correlated to a loss of anti-HIV-1 activity. Glycoproteomic identification of high-mannose proteins revealed a cohort of antiproteases shown to be important in HIV-1 resistance, whose expression covaried with the high-mannose signature. Our data strongly suggests high-mannose as a marker for secreted proteins mediating innate antiviral immunity in vaginal fluids and that drug formulation may impact this activity as reflected in the glycome.

Original languageEnglish (US)
Pages (from-to)1613-1622
Number of pages10
JournalACS Infectious Diseases
Volume4
Issue number11
DOIs
StatePublished - Nov 9 2018

Keywords

  • antiproteases
  • antiviral activity
  • cervicovaginal lavage
  • high-mannose
  • innate antiviral immunity
  • lectin microarray

ASJC Scopus subject areas

  • Infectious Diseases

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  • Cite this

    Koppolu, S., Wang, L., Mathur, A., Nigam, J. A., Dezzutti, C. S., Isaacs, C., Meyn, L., Bunge, K. E., Moncla, B. J., Hillier, S. L., Rohan, L. C., & Mahal, L. K. (2018). Vaginal Product Formulation Alters the Innate Antiviral Activity and Glycome of Cervicovaginal Fluids with Implications for Viral Susceptibility. ACS Infectious Diseases, 4(11), 1613-1622. https://doi.org/10.1021/acsinfecdis.8b00157