Secretion of HIV-1 cell entry inhibitors by lactobacilli

乳酸菌分泌 HIV-1 细胞进入抑制剂

• 批准号: 6892424
• 负责人: DANIEL BODEN
• 金额: $ 27.13万
• 依托单位: AARON DIAMOND AIDS RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892424
• 关键词: AIDS education /prevention; Lactobacillus; antiAIDS agent; bacterial genetics; biotherapeutic agent; drug screening /evaluation; genetic manipulation; human immunodeficiency virus 1; microorganism interaction; secretion; sexually transmitted diseases; technology /technique development; virus infection mechanism

DESCRIPTION (provided by applicant): Among the 4.2 million adults newly infected with HIV-1, almost 50 % were women. The increased incidence of HIV-1 infections in women, particularly those of childbearing age, underscores the urgent need for effective preventative and therapeutic options that are safe, affordable and culturally accepted. In the absence of an effective preventative vaccine, topical microbicides offer a practical alternative to block HIV-1 transmission at the site of entry, and may provide an useful and cost effective means for preventing spread of virus. Strains of lactobacillus were specifically selected because they can be easily seeded into the vaginal mucosa by oral ingestion, peri-anal transit, or by direct vaginal inoculation. Moreover, colonization with lactobacilli constitutes a normal part of the vaginal microflora, and may protect against the acquisition of sexually transmitted diseases, including HIV. Microbicides based on genetically engineered bacteria offer a significant advantage over other topical applied products in that they can be administered well before sexual contact, and may persist in the vaginal environment for several days following a single administration. The goal of this proposal is to test a panel of HIV-1 cell entry inhibitors, which are engineered for expression and secretion by lactobacilli, as functional microbicides against HIV-1 infection in vitro. Initial studies will focus on membrane fusion inhibitors T-20, T-1249, and 5-Helix. The specific aims of this study are: 1. To genetically engineer lactobacilli to express and secrete HIV-1 entry inhibitors. 2. To determine the antiviral potency of entry inhibitors secreted by Lactobacillus plantarum to inhibit HIV-1 infection. 3. To test naturally occurring human vaginal lactobacilli for effective secretion of entry inhibitors and to optimize their secretion capacity.

描述（由申请人提供）： 在新近感染HIV-1的420万成年人中，妇女近50％。妇女（尤其是育龄年龄）中，HIV-1感染的发病率增加，强调了迫切需要安全，负担得起和文化接受的有效预防和治疗选择。在没有有效的预防性疫苗的情况下，局部杀菌剂为阻止进入现场的HIV-1传输提供了一种实用的替代方法，并可能提供有用且具有成本效益的手段来防止病毒传播。特别选择了乳杆菌的菌株，因为它们可以通过口腔摄入，周日过境或直接通过阴道接种将它们轻松地播种到阴道粘膜中。此外，用乳杆菌定殖构成了阴道菌群的正常部分，可以防止收购包括HIV在内的性传播疾病。基于基因工程细菌的微生物比其他局部应用产品具有显着优势，因为它们可以在性接触之前很好地给药，并且在一次给药后可能会在阴道环境中持续几天。该提案的目的是测试一组HIV-1细胞进入抑制剂，该抑制剂是为乳酸杆菌的表达和分泌而设计的，作为抗HIV-1体外感染的功能性生液剂。最初的研究将集中于膜融合抑制剂T-20，T-1249和5-螺旋。这项研究的具体目的是： 1。遗传工程乳杆菌表达和分泌HIV-1进入抑制剂。 2。确定由乳杆菌分泌的抑制剂的抗病毒效力，以抑制HIV-1感染。 3。测试自然发生的人类阴道乳酸杆菌以有效分泌进入抑制剂并优化其分泌能力。