title: Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge.
abstract: Measures to prevent sexual mucosal transmission are critically needed, particularly to prevent transmission to young women at high risk in the microepidemics in South Africa that disproportionally contribute to the continued pandemic. To that end, microbicides containing anti-retroviral (ARV) agents have been shown to prevent transmission, but with efficacy limited both by adherence and pre-existing innate immune and inflammatory conditions in the female reproductive tract (FRT). Glycerol monolaurate (GML) has been proposed as a microbicide component to enhance efficacy by blocking these transmission-facilitating innate immune response to vaginal exposure. We show here in an especially rigorous test of protection in the SIV-rhesus macaque model of HIV-1 transmission to women, that GML used daily and before vaginal challenge protects against repeat high doses of SIV by criteria that include virological and immunological assays to detect occult infection. We also provide evidence for indirect mechanisms of action in GML-mediated protection. Developing a sustained formulation for GML delivery could contribute an independent, complementary protective component to an ARV-containing microbicide.
authors.affiliation: Department of Microbiology and Immunobiology, Medical School, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Rakasz
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Schultz-Darken
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, United States of America.
authors.forename: Karla
authors.initials: K
authors.lastname: Nephew
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, United States of America.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Weisgrau
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Cavan S
authors.initials: CS
authors.lastname: Reilly
authors.affiliation: Department of Microbiology and Immunobiology, Medical School, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunobiology, Medical School, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Southern
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Meghan
authors.initials: M
authors.lastname: Rothenberger
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Peterson
authors.affiliation: Department of Microbiology and Immunobiology, Medical School, University of Minnesota, Minneapolis, MN 55455, United States of America.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007848:Laurates / Q000494:pharmacology*; D008253:Macaca mulatta; D050178:Monoglycerides / Q000494:pharmacology*; D009092:Mucous Membrane / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D013019:South Africa; D014621:Vagina
chemical_list: D000890:Anti-Infective Agents; D044966:Anti-Retroviral Agents; D007848:Laurates; D050178:Monoglycerides; C020777:monolaurin