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156 A Live Microbicide Shows Efficacy in a Repeated Low Dose Challenge Model

Lagenaur, Laurel; Xu, Qiang; Lee, Peter P; Sanders-Beer, Brigitte E; Hamer, Dean H

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 64
doi: 10.1097/01.qai.0000397341.10482.9e
Abstracts
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NCI, 37 Convent Dr., Bethesda, MD 20892, USA

Women worldwide are at significant risk for HIV infection, with the mucosa of the cervix and vagina serving as a major portal for HIV entry. There is a critical need for effective female-controlled methods to prevent the sexual transmission of HIV that are applicable to the developing world. The genetic engineering of commensal bacteria to secrete anti-viral proteins at the mucosal surface presents one possible solution; however, the ability of such potential live microbicides to block infection in a relevant animal model has not been tested. We examined the ability of a recombinant human vaginal strain of Lactobacillus jensenii secreting the potent HIV-1 inhibitor cyanovirin-N to protect Chinese rhesus macaques against repeated low-dose vaginal challenges with SHIV (SF162P3). We challenged 24 hr after the last administration of the L. jensenii microbicide, to provide a stringent test of the durability (coital-independence) of the microbicide. The challenge dose of SHIV was 300 TCID50, which results in a 30% infection rate per exposure. We performed six challenges in a total of 20 macaques; 12 were colonized with the microbicide, with 8 uncolonized controls. In the 12 colonized animals, we found that inoculated L. jensenii (microbicide) bacterial loads were consistently high, >105 CFU/swab. Importantly, when exposed repeatedly to a low dose of SHIV, L. jensenii microbicide-inoculated animals showed a 57% reduction in infection rate (p = 0.037). In addition, we found that the plasma viral loads were modestly reduced in animals that had been colonized with L. jensenii microbicide (P < 0.02). These data demonstrate the feasibility of a live microbicide as a potent a durable approach to block heterosexual transmission of HIV in humans.

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