Lookup NU author(s): Dr Brian Ford
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
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
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
PubMed id: 24740100
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