EPITOPE MAPPING OF HIV-1 ENHANCING ANTIBODIES

在人类感染者的血清中频繁检测到 免疫缺陷病毒（HIV-1）的抗体增强感染性 HIV-1（EAb）的感染。这些血清中的EAb水平通常 超过病毒中和抗体（VNAb）水平。另 部分抗HIV-1阳性血清含有VNAb，但未检出 EAb，表明VNAb和EAb识别不同的表位上的 HIV-1的包膜糖蛋白（gp 120和gp 41）。EAb生成期间 HIV-1感染。用gp 120/gp 41免疫诱导的EAb可能 减少或消除其他抗体的保护效力 参与HIV-1中和和消除HIV-1， HIV-1感染细胞。HIV-1保护性免疫原的设计将是 通过以下方式促进：（1）鉴定EAb识别的表位，和（2） 了解病毒增强的机制。 我们建议定义参与增强HIV-1表达的gp 120/gp 41表位。 1单核细胞的感染性，使用：（a）抗肽抗血清和（B） 从人抗HIV阳性血清中分离的特异性抗体， 对连接到固体上的不同合成肽的亲和层析 支持.用于拟议研究的试剂可用（5）肽 （19-26个氨基酸残基长）从gp 120的几乎整个长度 和gp 41和相应的抗血清]。在建立 EAb的特异性，即感染性HIV-1抗体的进入位点 (Ab)复合物进入细胞将被定义为以下抑制 抗体对以下的作用：（a）HIV-1的CD 4（T4）受体;（B）Fc 受体;和（c）补体C3 b受体对α）感染性 和β）在不存在gp 120/gp 41的情况下gp 120/gp 41的摄取 和具有确定的表位特异性的EAb的存在。

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.