RHESUS MONOCLONAL ANTIBODIES TO SIV GLYCOPROTEINS

恒河猴 SIV 糖蛋白单克隆抗体

• 批准号: 6234936
• 负责人: JAMES E Robinson
• 金额: $ 20.68万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1998-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6234936
• 关键词: B lymphocyte; animal tissue; antibody neutralization test; antibody specificity; antiviral antibody; cooperative study; cross immunity; cryopreservation; enzyme linked immunosorbent assay; epitope mapping; genetic strain; glycoproteins; human immunodeficiency virus 1; human immunodeficiency virus 2; humoral immunity; immunoglobulin G; immunoglobulin idiotypes; live vaccine; monoclonal antibody; neutralizing antibody; simian immunodeficiency virus; tissue /cell culture; viral vaccines; virus antigen; virus envelope

The overall objective of this program is to define immune responses to SIV in Rhesus macaques which correlate with protective immunity with particular emphasis being placed on a comparison of antibody responses induced by vaccines derived from monocyte-tropic and T lymphocyte-tropic viruses. This subproject will probe humoral responses at the monoclonal antibody level in order to precisely identify epitopes or groups of epitopes which elicit potent neutralizing antibody responses in vivo in Rhesus macaques infected with experimental live SIV vaccines as well as in macaques manifesting long term survival of infection with pathogenic SIV strains. We will produce and characterize a large panel of rhesus monkey monoclonal antibodies (RhMAb) which reflect in vivo B cell recognition of SIV envelope glycoprotein epitopes. Each RhMAb will be characterized with respect to strain reactivity, binding to linear vs conformational epitopes, mapping of binding sites, and neutralizing activity. Since SIVmac, SIVmn and HIV-2 strains belong to the same group of lentiviruses and are serologically cross-reactive, it is likely that neutralizing epitopes in these viruses will be to some extent similar; however, it is far from certain whether there are important differences in the repertoire or function of neutralizing antibodies in each host species. This laboratory is involved in a parallel project to produce human MAbs to HIV-2 and thus we will have a unique opportunity to compare monoclonal antibody responses in both humans and macaques during chronic infections with a highly similar group of lentiviruses. We will also generate RhMAbs reactive with HIV-1 glycoproteins from macaques infected with chimeric SIV/HIV-1 (SHIV) vaccine constructs.

该计划的总体目的是将免疫反应定义为 与保护性免疫相关的恒河猕猴中的SIV与 特别强调抗体反应的比较 由源自单核细胞和T淋巴细胞诱导的疫苗诱导 病毒。 该子运动将在单克隆探测的体液响应 抗体水平以精确识别表位或组 在体内引起有效中和抗体反应的表位 感染了实验活体SIV疫苗的恒河猕猴以及 在猕猴中表现出致病性感染的长期存活 SIV菌株。 我们将产生并描述一大堆恒河馆 猴子单克隆抗体（RHMAB），反映了体内B细胞 识别SIV信封糖蛋白表位。 每个rhmab将是 根据应变反应性的特征，与线性VS结合 构象表位，结合位点的映射和中和 活动。 自SIVMAC，SIVMN和HIV-2菌株属于同一组 慢病毒和血清学交叉反应性，很可能 这些病毒中的中和表位将在某种程度上相似。 但是，远不能确定是否存在重要差异 在每个主机中中和抗体的曲目或功能中 物种。 该实验室参与了一个平行项目，以生产 人类的mabs到HIV-2，因此我们将有一个独特的机会来比较 慢性期间人类和猕猴的单克隆抗体反应 具有高度相似的慢病毒的感染。 我们也会 从猕猴感染的HIV-1糖蛋白中产生RHMABS 与嵌合SIV/HIV-1（SHIV）疫苗构建体。