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Macaque studies of vaccine and microbicide combinations for preventing HIV-1 sexual transmission

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dc.contributor.author Klasse, Per Johan
dc.contributor.author Dufour, Jason
dc.contributor.author Veazey, Ronald S.
dc.contributor.author Barouch, Dan H.
dc.contributor.author Moore, John P.
dc.date.accessioned 2012-11-15T19:14:29Z
dc.date.available 2012-11-15T19:14:29Z
dc.date.issued 2012-05
dc.date.submitted 2012-02
dc.identifier.issn 0027-8424
dc.identifier.issn 1091-6490
dc.identifier.uri http://hdl.handle.net/1721.1/74654
dc.description.abstract Vaccination and the application of a vaginal microbicide have traditionally been considered independent methods to prevent the sexual transmission of HIV-1 to women. Both techniques can be effective in macaque models, and limited efficacy has been observed in clinical trials for each. Here, we have addressed whether vaccines and microbicides can be used together to provide reinforced protection against virus challenge of rhesus macaques. In two separate experiments, four groups of animals were vaccinated with a T-cell–based adenovirus (Ad) vectored vaccine aimed at reducing postinfection viral loads and/or a partially effective dose of a vaginal microbicide aimed at blocking infection of a high-dose vaginal challenge with SIVmac251 or SHIV-162P3. In the first study, the only two protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors combined with the fusion inhibitor T-1249 as the vaginal microbicide before SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to significant reductions of both acquisition of infection and postinfection viral loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself reduced viral loads but had no acquisition effect, whereas the microbicide had a partial acquisition effect but minimal impact on viral loads. For both measures of protective efficacy, the vaccine–microbicide combination differed more from controls than did either separate intervention. Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately. en_US
dc.description.sponsorship Massachusetts Institute of Technology. Ragon Institute of MGH, MIT and Harvard en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Cooperative Agreement U19 AI76982) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant AI078526) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant AI066924) en_US
dc.language.iso en_US
dc.publisher National Academy of Sciences en_US
dc.relation.isversionof http://dx.doi.org/10.1073/pnas.1203183109 en_US
dc.source PNAS en_US
dc.title Macaque studies of vaccine and microbicide combinations for preventing HIV-1 sexual transmission en_US
dc.type Article en_US
dc.identifier.citation Barouch, D. H. et al. “Macaque Studies of Vaccine and Microbicide Combinations for Preventing HIV-1 Sexual Transmission.” Proceedings of the National Academy of Sciences 109.22 (2012): 8694–8698. ©2012 by the National Academy of Sciences en_US
dc.contributor.department Ragon Institute of MGH, MIT and Harvard en_US
dc.contributor.mitauthor Barouch, Dan H.
dc.relation.journal Proceedings of the National Academy of Sciences en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Final published version en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Barouch, D. H.; Klasse, P. J.; Dufour, J.; Veazey, R. S.; Moore, J. P. en


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