Lactobacilli: A Vaccine Delivery Vehicle for Women

描述（由申请人提供）：本申请是对 NIH 的回应 题为“艾滋病疫苗创新资助计划”的计划公告 通过R21机制进行研究”。艾滋病病毒（HIV）已被 在世界范围内不断传播。开发的困难之一 有效的疫苗在于病毒的粘膜传播。目前， 传统疫苗和口服疫苗都不足以诱导 阴道粘膜免疫。因此，本研究的目的是 开发一种能够阴道给药的基于细菌载体的疫苗。与一个 NIH 小额资助，我们成功建立了 基因克隆系统并为两者选择了基因表达盒 人阴道中外源抗原的细胞外和表面结合表达 乳酸杆菌。我们假设阴道乳酸杆菌可以被改造为 提供艾滋病毒疫苗。我们建议实现两个具体目标：1）克隆艾滋病毒 将抗原（gp120 和 gp41）包膜到阴道乳酸杆菌中并表达它们 既在细胞表面上又作为自由分泌的肽，并且 2) 评估 通过体外抗体测定和体内表达重组 HIV 抗原 体内诱导动物粘膜免疫。我们期望记录 使用乳酸杆菌将 HIV 抗原输送到阴道的可行性。 这项研究将是我们最初的 NIH 小额资助的重要下一步 项目。这对于实现我们的长期目标也至关重要 开发安全有效的粘膜疫苗来保护女性免受性侵害 艾滋病毒传播。

DESCRIPTION (Provided by Applicant): This application is in response to the NIH Program Announcement entitled "Innovative grant program for AIDS vaccine research " through the R21 mechanism. The AIDS virus, HIV, has been spreading continuously worldwide. One of the difficulties in developing an effective vaccine lies in the mucosal transmission of the virus. Currently, neither conventional vaccines nor oral vaccines are sufficient to induce mucosal immunity in the vagina. Therefore, the objective of this study is to develop a bacterial vector-based vaccine capable of vaginal delivery. With a NIH small grant, we have successfully established a gene-cloning system and selected a gene-expression cassette for both extracellular and surface-bound expression of foreign antigens in human vaginal lactobacilli. We hypothesize that vaginal lactobacilli can be engineered to deliver HIV vaccines. We propose to achieve two specific aims: 1) clone HIV envelope antigens (gp120 and gp41) into vaginal lactobacilli and express them both on the cell surface and as freely secreted peptides, and 2) evaluate the expression of recombinant HIV antigens by in vitro antibody assays and by in vivo induction of mucosal immunity in animals. We expect to document the feasibility of using lactobacilli to deliver HIV antigens to the vaginal tract. This study will be the important next step of our initial NIH small grant project. It will also be essential to attaining our long-term goal of developing a safe and effective mucosal vaccine to protect women against sexual HIV transmission.