TY - JOUR
T1 - Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge
AU - Haase, Ashley T.
AU - Rakasz, Eva
AU - Schultz-Darken, Nancy
AU - Nephew, Karla
AU - Weisgrau, Kimberly L.
AU - Reilly, Cavan S.
AU - Li, Qingsheng
AU - Southern, Peter J.
AU - Rothenberger, Meghan
AU - Peterson, Marnie L.
AU - Schlievert, Patrick M.
N1 - Publisher Copyright:
© 2015 Haase et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/6/9
Y1 - 2015/6/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84936857131&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0129465
DO - 10.1371/journal.pone.0129465
M3 - Article
C2 - 26057743
AN - SCOPUS:84936857131
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0129465
ER -
