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

 描述(申请人提供：该项目的总体目标是开发一种活的生物治疗产品(LBP)MucoCept-mCVN，通过增强阴道微生物组的抗病毒活性来保护妇女免受HIV-1感染。MucoCept-mCVN包含一种重组詹森乳杆菌阴道菌株，它定植在阴道黏膜上，并产生一种强大的HIV-1中和蛋白，改良的CV-V(MCV-N)。一旦整合到阴道微生物区系中，重组詹森氏乳杆菌菌株就会在阴道粘膜复制并结构性地产生MCV-N，阴道粘膜是女性感染HIV-1的主要部位。由于细菌可以持续存在于阴道，MucoCept-mCVN以一种性交独立的方式保护人们免受艾滋病毒-1的传播。这一产品概念的可行性已经在许多研究中得到了证实。创造了一种遗传稳定的重组詹森乳杆菌，菌株1153-1666，该菌株分泌具有生物学意义的广泛中和HIV-1进入抑制蛋白MCV-N。简氏乳杆菌1153-1666细菌已成功制成阴道崩解片(VDT)。Jensenii 1153-1666新鲜制备的培养物和片剂形式的配方细菌都被证明在反复的SHV阴道攻击模型中能够在阴道内定植恒河猴，在体内产生MCV-N，并保护猕猴免受SHV感染。拟议的SBIR 1期研究旨在为MucoCept-mCVN开发一种快速而简单的护理点(POC)诊断测试。由于不同女性的阴道微生物区系不同，而且随着时间的推移会发生变化，这项测试将允许女性监测mCVN的保护水平，以最大限度地发挥产品的有效性。

 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.