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

开发快速护理诊断，以监测 MucoCept-CVN（一种针对 HIV 的生物疗法）

基本信息

批准号：
9137087
负责人：
Laurel A. Lagenaur
金额：
$ 22.5万
依托单位：
OSEL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9137087
关键词：
Antiviral Agents Bacteria Biological Biological Response Modifier Therapy Buffers Cell Count Clinical Clinical Trials Cyanovirin-N Data Detection Development Devices Diagnostic Diagnostic tests Effectiveness Evaluation Female Future Genes Goals Grant HIV HIV Envelope Protein gp120 HIV-1 Human Immunoassay In Vitro Infection Intravaginal Administration Irrigation Lactobacillus Life Macaca Macaca mulatta Modeling Monitor Monoclonal Antibodies Mucous Membrane Phase Prevention strategy Proteins Recombinants Research Design Sampling Site Small Business Innovation Research Grant Swab Tablets Technology Testing User Compliance Vagina Validation Woman base cervicovaginal in vivo inhibitor/antagonist microbicide microbiome microbiota phase 1 study phase 2 study point of care point-of-care diagnostics prototype public health relevance rapid technique simian human immunodeficiency virus success transmission process vaginal fluid vaginal lactobacilli vaginal microbiome

项目摘要

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.

描述（通过应用程序提供：该项目的总体目标是开发一种实时的生物治疗产品（LBP），Mucocept-MCVN，通过增强阴道微生物组的抗病毒活性来保护女性免受HIV-1感染的影响。粘膜coccect-mcvn包含一种重组的阴道潜在的lactabacillus ancos and colinsenii and colys and co. HIV-1中和蛋白质的CV-V（MCV-N）曾掺入阴道菌群中，重组的jensenii菌株会在阴道中复制MCV-N。在许多研究中已经建立了这种产品概念。 Jensenii L. Jensenii 1153-1666细菌已成功表达为阴道分解的片剂（VDT）。两种新鲜制备的L. jensenii 1153-1666培养物和片剂形式的配方细菌都被证明可以在体内进行恒河猕猴，在体内产生MCV-N，并在反复的SHIV阴道挑战模型中保护猕猴免受Shiv感染。拟议的SBIR第1阶段研究旨在开发粘膜cvn的快速而简单的护理点（POC）诊断测试。由于阴道微生物群在女性之间有所不同，并且可以改变加班，因此该测试将使女性可以监测MCVN的保护水平，以最大程度地提高产品的有效性。