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EPITOPE MAPPING OF HIV-1 ENHANCING ANTIBODIES

HIV-1 增强抗体的表位作图

基本信息

批准号：
2064956
负责人：
A ROBERT ROBERT NEURATH
金额：
$ 20.19万
依托单位：
NEW YORK BLOOD CENTER
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-09-30 至 1995-07-31
项目状态：
已结题

项目摘要

The frequent detection in sera of humans infected with the human immunodeficiency virus (HIV-1) of antibodies enhancing the infectivity of HIV-1 (EAb) has been reported. The level of EAb in such sera usually exceeded the level of virus-neutralizing antibodies (VNAb). On the other hand, some anti-HIV-1 positive sera contained VNAb but no detectable EAb, suggesting that VNAb and EAb recognize distinct epitopes on the envelope glycoproteins (gp120 and gp41) of HIV-1. EAb generated during HIV-1 infection. EAb elicited by immunization with gp120/gp41 may diminish or abrogate the protective efficacy of other antibodies involved in HIV-=1 neutralization and in elimination of HIV-1 and of HIV-1 infected cells. The design of HIV-1 protective immunogens will be facilitated by: (1) identification of epitopes recognized by EAb and (2) understanding the mechanism of virus enhancement. We propose to define gp120/gp41 epitopes involved in enhancement of HIV- 1 infectivity for monocytes using: (a) anti-peptide antisera and (b) specific antibodies isolated from human anti HIV-positive sera by affinity chromatography on distinct synthetic peptides linked to a solid support. Reagents for the proposed research are available (5) peptides (19-26 amino acid residues long) from nearly the entire length of gp120 and gp41 and the corresponding antisera]. After establishing the specificity of EAb, the site of entry of the infectious HIV-1-antibody (Ab) complexes into cells will be defined by following the inhibitory effect of antibodies to: (a) the CD4 (T4) receptor for HIV-1; (b) Fc receptors; and (c) complement C3b receptors on alpha) the infectivity of HIV-1 Ab complexes and Beta) the uptake of gp120/gp41 in the absence and presence of EAb with defined epitope specificity.

人类感染者血清中的频繁检出免疫缺陷病毒(HIV-1)的抗体增强了传染性已经报告了HIV-1(EAB)的感染。这类血清中的EAB水平通常超过病毒中和抗体(VNAb)水平。另一方面另一方面，一些抗HIV-1阳性血清含有VNAb，但没有检测到 EAB，表明VNAb和EAB识别不同的表位 HIV-1囊膜糖蛋白(gp120和gp41)。期间生成的EAB HIV-1感染。用gp120/gp41免疫诱导的EAB可削弱或取消其他抗体的保护作用参与艾滋病毒-=1的中和和消除艾滋病毒-1和 HIV-1感染细胞。HIV-1保护性免疫原的设计将是促进：(1)识别EAB识别的表位和(2) 了解病毒增强的机制。我们建议定义gp120/gp41表位参与增强HIV- 1单核细胞感染性使用：(A)抗肽抗血清和(B) 从人抗HIV阳性血清中分离特异性抗体与固体相连的不同合成肽的亲和层析支持。建议研究的试剂是可用的(5)肽 (19-26个氨基酸残基)从几乎全长的gp120 和gp41及相应的抗血清。在建立了传染性HIV-1抗体进入部位EAB的特异性 (AB)进入细胞的复合体将通过以下抑制物定义抗HIV-1的CD4(T4)受体抗体的作用；(B)Fc 受体；和(C)补体C3b受体 HIV-1抗体复合体和β)在缺乏情况下对gp120/gp41的摄取以及具有定义的表位特异性的EAB的存在。