Targeting gp41 to elicit neutralizing antibodies against HIV-1

全球迫切需要开发针对HIV-1的保护性疫苗。中和抗体（Nabs） 可以有效预防HIV-1感染。然而，引发广泛反应的Nab 针对许多抗原多样性HIV-1分离株的抗体是一个重大挑战， HIV-1疫苗开发的障碍。拟议研究的主要目标是， 能够在粘膜表面上引发广泛反应性Nab的新型抗原，其长期目标是 研制针对这种病毒的疫苗具体来说，我们建议靶向膜近端外部 通过产生表达抗原性完整的重组乳酸菌（LAB）， 使用一种新技术在细胞表面上产生gp 41蛋白片段。本建议的范围仅限于 具体目的如下：（1）产生在细胞表面展示HIV-1 gp 41 MPER的重组干酪乳杆菌， 细胞表面，（2）设计最佳疫苗策略并评估 重组L. casei，以及（3）在XenoMouse中引发针对HIV-1 gp 41 MPER的广泛反应性Nab。 这项研究的成功完成将产生新的疫苗候选人和策略， 保护性体液免疫反应，这将是艾滋病疫苗向前迈出的一大步 发展努力。

There is a global urgency to develop a protective vaccine against HIV-1. Neutralizing antibodies (Nabs) can provide effective prophylaxis against HIV-1 infections. However, eliciting Nabs that are broadly reactive against many antigenically diverse HIV-1 isolates has been a major challenge and it remains a critical roadblock to HIV-1 vaccine development. The primary objective of the studies being proposed is to generate novel antigens that are able to elicit broadly reactive Nabs on the mucosal surface, with a long-term goal of developing a vaccine against the virus. Specifically, we propose to target the membrane-proximal external region (MPER) of gp41 by generating recombinant lactic acid bacteria (LAB) that express antigenically intact gp41 protein fragments on the cell surface using a novel technology. The scope of this proposal is limited to the following specific aims: (1) to generate recombinant Lactobacillus casei that display HIV-1 gp41 MPER on the cell surface, (2) to devise an optimal vaccine strategy and to evaluate immunogenic properties of recombinant L. casei in mice, and (3) to elicit broadly reactive Nabs against HIV-1 gp41 MPER in XenoMouse. Successful completion of this study will generate novel vaccine candidates and strategies for eliciting protective humoral immune responses, which would represent a major step forward in AIDS vaccine development efforts.