The overall goal of this project is to develop a live biotherapeutic product (LBP), MucoCept-mCVN, to protect women from HIV-1 infection by enhancing the antiviral activity of the Vaginal microbiome. MucoCept- mCVN contains a recombinant Vaginal strain of Lactobacillus jensenii that colonizes the Vaginal Mucosa and produces a potent HIV-1-neutralizing protein, modified CV-V (mCV-N). Once incorporated into the Vaginal microbiota, the recombinant L. jensenii strain replicates and constitutively produces mCV-N in the Vaginal Mucosa, the primary site of HIV-1 infection in women. Since the Bacteria can persist in the Vagina, MucoCept- mCVN protects against HIV-1 Transmission in a coitally independent manner. The feasibility of this product concept has been established in a number of studies. a genetically stable recombinant L. jensenii, strain 1153- 1666, was created that secretes biologically significant levels of a broadly neutralizing HIV-1 entry inhibitor protein, mCV-N. The L. jensenii 1153-1666 Bacteria have been successfully formulated as a vaginally disintegrating tablet (VDT). Both freshly prepared cultures of L. jensenii 1153-1666 and the formulated Bacteria in tablet form have been shown to vaginally colonize Rhesus macaques, produce mCV-N in vivo, and protect macaques against SHIV infection in a repeated SHIV Vaginal challenge model. The proposed SBIR Phase 1 studies are designed to develop a Rapid and simple Point of Care (POC) Diagnostic test for MucoCept-mCVN. Since the Vaginal microbiota differs among women and can change overtime, this test will allow women to monitor protective levels of mCVN to maximize the effectiveness of the product.
Public Health Relevance Statement: Public Health Relevance: We are developing a fundamentally new female-controlled and coital-independent HIV Preventative strategy for women using a colonizing recombinant Vaginal Lactobacillus jensenii that produces a potent HIV-1-neutralizing protein, modified CV-V (mCV-N). Since the Vaginal microbiota differs among women and can change overtime, this, in this Grant we will develop simple Point of Care Diagnostic test to allow women to monitor protective levels of mCVN to maximize the effectiveness of the product.
