Novel Chimeric Env Glycoproteins for AIDS Vaccines

用于艾滋病疫苗的新型嵌合包膜糖蛋白

• 批准号: 6845190
• 负责人: LING YE
• 金额: $ 22.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845190
• 关键词: AIDS vaccines; DNA; HIV envelope protein; antigen antibody reaction; biotechnology; cell membrane; chimeric proteins; cross immunity; gene expression; gene mutation; genetically modified animals; guinea pigs; hemagglutinin; immunization; immunogenetics; laboratory mouse; membrane proteins; monoclonal antibody; neutralizing antibody; protein engineering; protein structure function; protein transport; vaccine development; vaccine evaluation; viruslike particle

DESCRIPTION (provided by applicant): The development of an effective AIDS vaccine is in urgent need for the control of the rapid spread of HIV infection. The focus of this project is to explore novel vaccine design strategies for eliciting cross-reactive beutralizing antibody responses against HIV. The Env protein of HIV is synthesized as an Gp160 precursor and processed into the surface subunit (SU) Gp120 and the transmembrane subunit (TM) Gp41. The SU protein mediates interaction with the receptor molecule CD4 as well as co-receptor molecules such as CCR5 and CXCR4, while the TM protein anchors the envelope glycoprotein on viral or cell membranes and mediates fusion between viral and cellular membranes for virus entry. It has been shown that the TM protein contains conserved neutralizing epitopes. In this study, we plan to construct novel chimeric proteins between the influenza hemmagglutini (HA) and the HIV TM protein (Gp41) and investigate whether such chimeric proteins will be advantageous in eliciting neutralizing antibodies against the HIV envelope protein. Specifically, we will first construct a series of chimeric protein and characterize their surface expression as well as reactivity of antibodies directed against the HIV TM protein. We will then evaluate immunogenicities of the candidate chimeric proteins in small laboratory models (mice and guinea pigs) in the context of DNA immunization or VLP immunization. We will also test the effectiveness of different priming-boosting protocols in eliciting cross-reactive neutralizing antibodies against HIV.

描述（由申请人提供）：有效的艾滋病疫苗的开发迫切需要控制艾滋病毒感染的快速传播。该项目的重点是探索新型的疫苗设计策略，以引起对HIV的交叉反应性抗体反应。 HIV的ENV蛋白合成为GP160前体，并加工到表面亚基（SU）GP120和跨膜亚基（TM）GP41中。 SU蛋白介导了与受体分子CD4以及诸如CCR5和CXCR4等共受体分子的相互作用，而TM蛋白将包膜糖蛋白锚定在病毒或细胞膜上，并介导病毒和细胞膜之间的融合，以供病毒进入病毒膜。已经表明，TM蛋白包含保守的中和表位。在这项研究中，我们计划在流感的Hemmagglutini（HA）和HIV TM蛋白（GP41）之间构建新型的嵌合蛋白（GP41），并研究这种嵌合蛋白是否会在激发中和对HIV INVELOPE蛋白的中和抗体中有利。 具体而言，我们将首先构建一系列嵌合蛋白，并表征其表面表达以及针对HIV TM蛋白的抗体的反应性。然后，我们将在小型实验室模型（小鼠和豚鼠）中评估候选嵌合蛋白的免疫原性。我们还将测试不同引发方案在引发抗HIV的交叉反应中和抗体中的有效性。