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MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa

Calenda, Giulia PhD; Villegas, Guillermo MS; Barnable, Patrick BS; Litterst, Claudia PhD; Levendosky, Keith BS; Gettie, Agegnehu MS; Cooney, Michael L. MS; Blanchard, James PhD; Fernández-Romero, José A. PhD; Zydowsky, Thomas M. PhD; Teleshova, Natalia MD, PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 01 March 2017 - Volume 74 - Issue 3 - p e67–e74
doi: 10.1097/QAI.0000000000001167
Basic Science

Abstract: The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian–human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

*Population Council, New York, NY;

BioRad Laboratories, Hercules, CA;

Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY; and

§Tulane National Primate Research Center, Tulane University, Covington, LA.

Correspondence to: Natalia Teleshova, MD, PhD, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065 (e-mail: nteleshova@popcouncil.org).

Supported by the US President's Emergency Plan for AIDS Relief (PEPFAR) through the US Agency for International Development (USAID) Cooperative Agreement (GPO-A-00-04-00019-00, www.usaid.gov) and from the Tulane National Primate Research Center (Primate Center base grant P51 OD011104, http://tulane.edu/tnprc).

The authors have no funding or conflicts of interest to disclose.

G. C. and G. V. contributed equally.

Received March 07, 2016

Accepted July 15, 2016

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.