SYNTHETIC HIV-1 ENV PROTEIN ANALOGS FOR FUTURE VACCINES

用于未来疫苗的合成 HIV-1 ENV 蛋白类似物

• 批准号: 3185499
• 负责人: A ROBERT ROBERT NEURATH
• 金额: $ 26.3万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-11-07 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185499
• 关键词: AIDS; AIDS vaccines; B lymphocyte; affinity chromatography; antibody neutralization test; antiviral antibody; cross immunity; glycoproteins; helper T lymphocyte; human immunodeficiency virus 1; human tissue; immunological substance; laboratory rabbit; peptide chemical synthesis; protein engineering; radioimmunoassay; synthetic antigens; synthetic peptide; synthetic vaccines; virus antigen; virus envelope; virus protein

DESCRIPTION: (Adapted from the applicant's abstract) The goal of this proposal is to design immunogens for preventing infections with the human immunodeficiency virus (HIV-1). Such immunogens are expected to elicit immune responses eliminating HIV-1 and HIV-infected cells both of which can transmit disease. The components of such a response include: (1) antibodies which: (a) are virus-neutralizing (VNAb) and (b) participate in antibody- and complement-mediated cytotoxicity (ADCC and ACC, the production of which is dependent on generations of specific helper T (Th) cells; and (2) cytotoxic T (Tc) cells. The high variability in the sequence of HIV-1 envelope glycoproteins gp120 and gp41 between distinct HIV-1 isolates and the subtype specificity of early VNAb responses suggested that the production of broadly protective HIV-1 immunogens may be difficult. They propose to design multicomponent synthetic peptide immunogens eliciting broad VNAb, ADCC, ACC and HIV-1-specific Th and Tc cell responses. To select the appropriate peptides for such immunogens, they propose to carry out detailed studies on the immunochemical cross-reactivity between selected B- and T-cell epitopes of HIV-1 glycoproteins gp120/gp41 considering both the sequence variability in these viral proteins and the HLA restriction of immune responsiveness to these epitopes. The components of the proposed immunogens include: peptides corresponding to (a) hypervariable loops of the gp120 sequence (corresponding to residues 303-338 in the isolate IIIB) selected on the basis of immunological cross-reactivity from a limited number of HIV-1 isolates; (b) major T helper cell determinants; and (c) one or two additional peptides eliciting virus-neutralizing and/or cytotoxic antibodies.

描述：（根据申请人的摘要进行了改编） 提案是设计用于预防人类感染的免疫原分 免疫缺陷病毒（HIV-1）。 这种免疫原子有望引起 消除HIV-1和HIV感染细胞的免疫反应都可以 传播疾病。 这种响应的组成部分包括：（1） 抗体：（a）是病毒中和（vnab）和（b）参与 抗体和补体介导的细胞毒性（ADCC和ACC， 其产生取决于特定辅助者t（th）的几代 细胞； （2）细胞毒性T（TC）细胞。 HIV-1包膜糖蛋白GP120的序列的高变异性 与不同的HIV-1分离株和亚型特异性之间的GP41 早期的VNAB回应表明，生产广泛保护性 HIV-1免疫原可能很困难。 他们建议设计多组件 合成的肽免疫原，引起广泛的VNAB，ADCC，ACC和 HIV-1特异性TH和TC细胞反应。 选择适当的 他们建议进行这种免疫原的肽，他们建议进行有关的详细研究 选定的B-和T细胞表位之间的免疫化学交叉反应性 HIV-1糖蛋白GP120/GP41的序列可变性 在这些病毒蛋白以及HLA对免疫反应性的限制 这些表位。 拟议的免疫原子的成分包括： 对应于（a）GP120序列的高变量环的肽 （对应于分离物IIIB中的残基303-338）在 来自有限数量的HIV-1的免疫交叉反应基础 分离株； （b）主要的T辅助细胞决定因素； （c）一两个 其他引起病毒中和和/或细胞毒性的肽 抗体。