Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge

Ashley T. Haase, Eva Rakasz, Nancy Schultz-Darken, Karla Nephew, Kimberly L. Weisgrau, Cavan S. Reilly, Qingsheng Li, Peter J. Southern, Meghan Rothenberger, Marnie L. Peterson, Patrick M. Schlievert

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0129465
JournalPloS one
Volume10
Issue number6
DOIs
StatePublished - Jun 9 2015

Fingerprint

Anti-Infective Agents
glycerol
anti-infective agents
dosage
Anti-Retroviral Agents
Pandemics
pandemic
South Africa
Human immunodeficiency virus 1
Macaca mulatta
immunoassays
Innate Immunity
HIV-1
mechanism of action
Assays
monolaurin
Infection
infection
testing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Haase, A. T., Rakasz, E., Schultz-Darken, N., Nephew, K., Weisgrau, K. L., Reilly, C. S., ... Schlievert, P. M. (2015). Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge. PloS one, 10(6), [e0129465]. https://doi.org/10.1371/journal.pone.0129465

Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge. / Haase, Ashley T.; Rakasz, Eva; Schultz-Darken, Nancy; Nephew, Karla; Weisgrau, Kimberly L.; Reilly, Cavan S.; Li, Qingsheng; Southern, Peter J.; Rothenberger, Meghan; Peterson, Marnie L.; Schlievert, Patrick M.

In: PloS one, Vol. 10, No. 6, e0129465, 09.06.2015.

Research output: Contribution to journalArticle

Haase, AT, Rakasz, E, Schultz-Darken, N, Nephew, K, Weisgrau, KL, Reilly, CS, Li, Q, Southern, PJ, Rothenberger, M, Peterson, ML & Schlievert, PM 2015, 'Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge', PloS one, vol. 10, no. 6, e0129465. https://doi.org/10.1371/journal.pone.0129465
Haase AT, Rakasz E, Schultz-Darken N, Nephew K, Weisgrau KL, Reilly CS et al. Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge. PloS one. 2015 Jun 9;10(6). e0129465. https://doi.org/10.1371/journal.pone.0129465
Haase, Ashley T. ; Rakasz, Eva ; Schultz-Darken, Nancy ; Nephew, Karla ; Weisgrau, Kimberly L. ; Reilly, Cavan S. ; Li, Qingsheng ; Southern, Peter J. ; Rothenberger, Meghan ; Peterson, Marnie L. ; Schlievert, Patrick M. / Glycerol monolaurate microbicide protection against repeat high-dose SIV vaginal challenge. In: PloS one. 2015 ; Vol. 10, No. 6.
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