Development of a rapid point of care diagnostic,to monitor MucoCept-CVN, an HIV-targeted biotherapy,

 描述（由申请人提供：本项目的总体目标是开发一种活生物素产品（LBP）MucoCept-mCVN，通过增强阴道微生物组的抗病毒活性来保护女性免受HIV-1感染。MucoCept- mCVN含有一种重组的詹氏乳杆菌阴道菌株，该菌株定殖于阴道粘膜并产生一种有效的HIV-1中和蛋白，即修饰的CV-V（mCV-N）。重组L. jensenii株在阴道粘膜中复制并组成性产生mCV-N，阴道粘膜是女性HIV-1感染的主要部位。由于细菌可以在阴道中持续存在，MucoCept- mCVN以不依赖性交的方式防止HIV-1传播。该产品概念的可行性已在多项研究中得到证实。一个遗传稳定的重组L. jensenii，菌株1153- 1666，其分泌生物学上显著水平的广泛中和HIV-1进入抑制蛋白mCV-N。洛杉矶Jensenii 1153-1666细菌已成功地配制成阴道崩解片（VDT）。两种新鲜制备的L. jensenii 1153-1666和片剂形式的配制细菌已显示在恒河猴阴道定殖，在体内产生mCV-N，并在重复的SHIV阴道攻击模型中保护恒河猴免受SHIV感染。拟定的SBIR I期研究旨在开发MucoCept-mCVN的快速、简单的床旁（POC）诊断检测。由于女性的阴道微生物群不同，并且会随着时间的推移而变化，因此这项测试将允许女性监测mCVN的保护水平，以最大限度地提高产品的有效性。

 DESCRIPTION (provided by applicant: 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.