Lactobacilli: A Vaccine Delivery Vehicle for Women

描述(申请人提供)：本申请是对美国国立卫生研究院的回应 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，艾滋病毒，已经被 在全球范围内持续蔓延。开发一个应用程序的困难之一 有效的疫苗在于病毒的粘膜传播。目前， 无论是传统疫苗还是口服疫苗都不足以诱导 阴道中的粘膜免疫。因此，这项研究的目的是 开发一种能够经阴道传递的细菌载体疫苗。使用一个 NIH小额赠款，我们已经成功地建立了一个 建立了基因克隆系统，并为两者选择了基因表达盒 外源抗原在人阴道中的细胞外和表面结合表达 乳酸菌。我们假设阴道乳杆菌可以被改造成 提供艾滋病毒疫苗。我们计划实现两个具体目标：1)克隆HIV 包膜抗原(gp120和gp41)进入阴道乳杆菌并表达 在细胞表面和作为自由分泌的多肽，以及2)评估 用体外抗体测定法和免疫印迹法表达重组HIV抗原 活体诱导动物的粘膜免疫。我们预计将记录 利用乳酸菌将HIV抗原输送到阴道的可行性。 这项研究将是我们最初的NIH小额赠款的重要下一步 项目。它对实现我们的长期目标也是至关重要的 开发一种安全有效的黏膜疫苗来保护女性免受性侵犯 艾滋病毒的传播。

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.