Lactobacilli: A Vaccine Delivery Vehicle for Women

描述（由申请人提供）：本申请是对NIH 题为“艾滋病疫苗创新赠款方案"的方案公告 通过R21机制进行研究。艾滋病病毒，HIV， 在全球范围内不断传播。开发一个 有效的疫苗在于病毒的粘膜传播。目前， 常规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细菌载体疫苗。与 我们成功地建立了一个 基因克隆系统，并选择了一个基因表达盒， 外源抗原在人阴道组织中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成 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 将囊膜抗原（gp 120和gp 41）导入阴道乳杆菌中并表达它们 在细胞表面上和作为自由分泌的肽，和2）评估 通过体外抗体测定和体内抗体测定表达重组HIV抗原 在动物体内诱导粘膜免疫。我们希望记录下 使用乳酸杆菌将HIV抗原递送到阴道的可行性。 这项研究将是我们最初的NIH小额资助的重要下一步 项目这对实现我们的长期目标也至关重要， 开发一种安全有效的粘膜疫苗，保护妇女免受性侵犯。 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.