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  • 标题:Crosslinked HIV-1 envelope–CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques
  • 本地全文:下载
  • 作者:Timothy Fouts ; Karla Godfrey ; Kathryn Bobb
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2002
  • 卷号:99
  • 期号:18
  • 页码:11842-11847
  • DOI:10.1073/pnas.182412199
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The identification of HIV envelope structures that generate broadly cross-reactive neutralizing antibodies is a major goal for HIV-vaccine development. In this study, we evaluated one such structure, expressed as either a gp120-CD4 or a gp140-CD4 complex, for its ability to elicit a neutralizing antibody response. In rhesus macaques, covalently crosslinked complexes of soluble human CD4 (shCD4) and HIV-1IIIB envelope glycoproteins (gp120 or gp140) generated antibodies that neutralized a wide range of primary HIV-1 isolates regardless of the coreceptor usage or genetic subtype. Ig with cross-reactive neutralizing activity was recovered by affinity chromatography with a chimeric single-chain polypeptide containing sequences for HIVBaL gp120 and a mimetic peptide that induces a CD4-triggered envelope structure. These results suggest that covalently crosslinked complexes of the HIV-1 surface envelope glycoprotein and CD4 elicit broadly neutralizing humoral responses that, in part, may be directed against a novel epitope(s) found on the HIV-1 envelope.
  • 关键词:gp120‖gp140‖gp120–CD4 complex‖vaccine
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