156 A Live Microbicide Shows Efficacy in a Repeated Low Dose Challenge ModelLagenaur, Laurel; Xu, Qiang; Lee, Peter P; Sanders-Beer, Brigitte E; Hamer, Dean HJAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 64 doi: 10.1097/01.qai.0000397341.10482.9e Abstracts Free Author InformationAuthors Article MetricsMetrics 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.Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.