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PLoS One. 2014 Apr 16;9(4):e94547. doi: 10.1371/journal.pone.0094547. eCollection 2014.

A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV.

Author information

1
Center for Biomedical Research, Population Council, New York, New York, United States of America.
2
Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, United States of America.
3
Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
4
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc. (Formerly SAIC-Frederick, Inc.), Frederick National Laboratory, Frederick, Maryland, United States of America.
5
Instituto de Virología J.M.Vanella-Facultad de Ciencias Médicas-Universidad Nacional de Córdoba, Córdoba, Argentina.
6
Center for Biomedical Research, Population Council, New York, New York, United States of America; Instituto de Virología J.M.Vanella-Facultad de Ciencias Médicas-Universidad Nacional de Córdoba, Córdoba, Argentina.

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 MIV-150, zinc acetate (ZA) and carrageenan (CG) 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 5×10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8×10(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.

PMID:
24740100
PMCID:
PMC3989196
DOI:
10.1371/journal.pone.0094547
[Indexed for MEDLINE]
Free PMC Article

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