title: A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV.
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.
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Larisa
authors.initials: L
authors.lastname: Kizima
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Aixa
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kenney
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Nina
authors.initials: N
authors.lastname: Derby
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Olga
authors.initials: O
authors.lastname: Mizenina
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Radhika
authors.initials: R
authors.lastname: Menon
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Samantha
authors.initials: S
authors.lastname: Seidor
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Keith
authors.initials: K
authors.lastname: Levendosky
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Ninochka
authors.initials: N
authors.lastname: Jean-Pierre
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Pavel
authors.initials: P
authors.lastname: Pugach
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Villegas
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Ford
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, United States of America.
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.affiliation: Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc. (Formerly SAIC-Frederick, Inc.), Frederick National Laboratory, Frederick, Maryland, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc. (Formerly SAIC-Frederick, Inc.), Frederick National Laboratory, Frederick, Maryland, United States of America.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Instituto de Virología J.M.Vanella-Facultad de Ciencias Médicas-Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Paglini
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Natalia
authors.initials: N
authors.lastname: Teleshova
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zydowsky
authors.affiliation: Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
authors.affiliation: 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.
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández-Romero
mesh_terms: D052685:Alphapapillomavirus / Q000187:drug effects* / Q000502:physiology; D001003:Anal Canal / Q000187:drug effects / Q000821:virology; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D002351:Carrageenan / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005782:Gels; D006367:HeLa Cells; D006561:Herpes Simplex / Q000517:prevention & control / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D008807:Mice, Inbred BALB C; D030361:Papillomavirus Infections / Q000517:prevention & control / Q000821:virology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D012007:Rectum / Q000187:drug effects / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D016896:Treatment Outcome; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014621:Vagina / Q000187:drug effects / Q000821:virology; D019345:Zinc Acetate / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D005782:Gels; C510296:MIV 150; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D014508:Urea; D002351:Carrageenan; D019345:Zinc Acetate
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