Toggle Main Menu Toggle Search

Open Access padlockePrints

A Potent Combination Microbicide that Targets SHIV-RT, HSV-2 and HPV

Lookup NU author(s): Dr Brian Ford

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing (M) under bar IV-150, zinc acetate ((Z) under barA) and carrageenan ((C) under barG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (p = 0.0187) infection of mice when 10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when 5x10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8x10(6) HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use.


Publication metadata

Author(s): Kizima L, Rodriguez A, Kenney J, Derby N, Mizenina O, Menon R, Seidor S, Zhang SM, Levendosky K, Jean-Pierre N, Pugach P, Villegas G, Ford BE, Gettie A, Blanchard J, Piatak M, Lifson JD, Paglini G, Teleshova N, Zydowsky TM, Robbiani M, Fernandez-Romero JA

Publication type: Article

Publication status: Published

Journal: PLOS ONE

Year: 2014

Volume: 9

Issue: 4

Online publication date: 16/04/2014

Acceptance date: 17/03/2014

Date deposited: 06/04/2018

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pone.0094547

DOI: 10.1371/journal.pone.0094547

PubMed id: 24740100


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share