Fouts Timothy, Godfrey Karla, Bobb Kathryn, Montefiori David, Hanson Carl V, Kalyanaraman V S, DeVico Anthony, Pal Ranajit
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA.
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11842-7. doi: 10.1073/pnas.182412199. Epub 2002 Aug 21.
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-1(IIIB) 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 HIV(BaL) 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.
鉴定能产生广泛交叉反应性中和抗体的HIV包膜结构是HIV疫苗研发的主要目标。在本研究中，我们评估了一种这样的结构，其以gp120-CD4或gp140-CD4复合物形式表达，以研究其引发中和抗体反应的能力。在恒河猴中，可溶性人CD4（shCD4）与HIV-1（IIIB）包膜糖蛋白（gp120或gp140）的共价交联复合物产生了能中和多种原发性HIV-1分离株的抗体，而不论其共受体使用情况或基因亚型如何。通过用包含HIV（BaL）gp120序列和诱导CD4触发包膜结构的模拟肽的嵌合单链多肽进行亲和层析，回收了具有交叉反应性中和活性的Ig。这些结果表明，HIV-1表面包膜糖蛋白与CD4的共价交联复合物引发了广泛的中和体液反应，部分可能针对HIV-1包膜上发现的新表位。
