Antigen Design, Production and Vaccine Development

研究的主要目标是设计HIV-1包膜抗原， 广泛反应性中和抗体（Nabs），长期目标是开发一种保护性抗体， 针对病毒的疫苗我们采取了双管齐下的方法，靶向gp 41膜近端， 外部区域（MPER）和gp 120的外部结构域（gp 120 OD）。我们制造了两个原型 基于可溶性形式的gp 41 MPER和gp 1200 D的抗原，所述gp 41 MPER和gp 1200 D源自M组共有包膜。 这两种蛋白质都可以在小鼠中引发针对多种主要HIV-1分离株的Nab。我们的目标是利用现有的和 不断发展对原型抗原的生物化学、结构和免疫原性的理解， 设计第二代抗原，可以诱导更有效的Nab。为了实现这一目标，我们 组建一个强大的、互补的、协作的、具有结构生物学专业知识的研究团队， 病毒学、蛋白质生物化学、分子生物学、免疫学和疫苗学。该委员会的具体目标 项目1是：（1）更好地确定gp 41 MPER上的B细胞表位，（2）提高 gp 41 MPER上的中和表位，和（3）基于以下开发和评估抗原的免疫原性： gp120OD。成功完成拟议的研究将是朝着以下目标迈进的一个重大进展： 开发一种保护性的艾滋病疫苗

The major objective of the studies being proposed is to design HIV-1 envelope antigens that can elicit broadly reactive neutralizing antibodies (Nabs), with a long-term goal of developing a protective vaccine against the virus. We are taking a two-pronged approach of targeting gp41 membrane proximal external region (MPER) and the outer domain of gp120 (gp120OD). We have generated two prototypic antigens based on soluble form of gp41 MPER and gp1200D derived from M group consensus envelope. Both proteins can elicit Nabs against multiple primary HIV-1 isolates in mice. Our goal is to use current and evolving understanding of biochemical, structural and immunogenic properties of the prototypic antigens to design second-generation antigens that could induce even more potent Nabs. To achieve the goal, we have put together a strong, complementary, collaborative team of investigators with expertise in structural biology, virology, protein biochemistry, molecular biology, immunology and vaccinology. The specific aims of the Project 1 are: (1) to better define B cell epitopes on gp41 MPER, (2) to improve immunogenicity of neutralizing epitopes on gp41 MPER, and (3) to develop and evaluate immunogenicity of antigens based on gp120OD. Successful completion of the proposed studies would represent a major advancement towards developing a protective AIDS vaccine.