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.

Conflict of interest statement

Competing Interests: PMS is co-founder of a small business, Hennepin Life Sciences, which has licensed a patent awarded to the University of Minnesota for the development of glycerol monolaurate (GML) to treat vaginal bacterial infections. PMS receives no salary or consulting support from Hennepin Life Sciences, though he does have stock in the company. PMS and MLP are co-inventors on the above GML patent awarded to the University of Minnesota. The title of this patent is: Compositions and Methods for Controlling Infections (US 8796332 B2). The authors confirm that the patent and stock do not alter adherence to all PLOS ONE policies on sharing data and materials.