Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response
Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response
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DOI：
10.1016/j.vaccine.2004.09.037
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发表时间：
2005-02-18
期刊：
影响因子：
5.5
通讯作者：
MacDonald, KS
中科院分区：
文献类型：
--
作者：
Ho, J;Uger, RA;MacDonald, KS
2F5是少数几种对I型人类免疫缺陷病毒（HIV - 1）具有广泛中和作用的单克隆抗体之一。它识别gp41中的氨基酸序列ELDKWAS。我们先前已经确定了一些具有免疫靶向性的2F5反应性候选免疫原。其中三个（命名为H - BT1 - 3）在免疫球蛋白重链的P - 转角位点对ELDKWAS序列进行了约束。另外两个（L - CT和L - CTx3）将该序列连接在免疫球蛋白轻链的C末端，且构象约束极小。在本次研究中，发现H - BTs与2F5的结合亲和力比其无约束的对应物高出多达10倍。当用作免疫原时，无论是否使用佐剂都能诱导出免疫原特异性抗体，这证实了这些免疫原构建体的免疫靶向潜力。虽然诱导出了HIV - 1 gp160交叉反应性抗体，但未检测到病毒中和作用。因此，在设计基于2F5的疫苗时，除2F5结合亲和力之外的其他因素可能起着关键作用。（c）2004爱思唯尔有限公司。保留所有权利。
2F5 is one of the few broadly neutralizing monoclonal antibodies against type I Human Immunodeficiency Virus (HIV-1). It recognizes the amino acid sequence ELDKWAS in gp41. We have previously identified a number of immunotargeting 2F5-reactive candidate immunogens. Three of them (designated H-BT1-3) have the ELDKWAS sequence constrained at P-turn sites within the immunoglobulin heavy chain. Two others (L-CT and L-CTx3) have the sequence attached at the C-terminus of the immunoglobulin light chain with minimal conformational constraints. In the present investigation, the H-BTs were found to bind 2F5 with up to 10-fold higher affinities than their unconstrained counterpart. When used as immunogens, immunogen-specific antibodies were induced with or without adjuvant, confirming the immunotargeting potential of these immunogen constructs. While HIV-1 gp 160 cross-reactive antibodies were induced, virus neutralization was not detected. Thus, factors other than 2175 binding affinity may have a critical role to play in the design of a 2F5-based vaccine. (c) 2004 Elsevier Ltd. All rights reserved.