IN-VITRO EVOLUTION OF A NEUTRALIZING HUMAN-ANTIBODY TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO ENHANCE AFFINITY AND BROADEN STRAIN CROSS-REACTIVITY
IN-VITRO EVOLUTION OF A NEUTRALIZING HUMAN-ANTIBODY TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO ENHANCE AFFINITY AND BROADEN STRAIN CROSS-REACTIVITY
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DOI：
10.1073/pnas.91.9.3809
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发表时间：
1994-04-26
影响因子：
11.1
通讯作者：
BURTON, DR
中科院分区：
文献类型：
--
作者：
BARBAS, CF;HU, D;BURTON, DR
描述了允许改善抗体亲和力的方法。这种方法称为互补决定区（CDR）步移，不需要抗体或抗原的结构信息。靶向互补决定区进行随机诱变，然后通过噬菌体展示方法选择适合性，在这种情况下增加结合亲和力。目前的研究目标是人CD4结合位点抗gp120抗体，该抗体具有强效和广泛的中和作用。这种抗体亲和力的演变表明，在这种情况下，亲和力可以增加，同时对人类免疫缺陷病毒1型变体的反应性变宽。经人免疫缺陷病毒1型的实验室和初级临床分离株测定，该抗体的中和能力得到提高。产生具有特殊亲和力和广泛中和能力的人抗体的能力对于人免疫缺陷病毒1型感染的抗体的治疗性和预防性应用具有意义。
A method is described that allows for the improvement of antibody affinity. This method, termed complementary-determining region (CDR) walking, does not require structural information on either antibody or antigen. Complementary-determining regions are targeted for random mutagenesis followed by selection for fitness, in this case increased binding affinity, by the phage-display approach. The current study targets a human CD4-binding-site anti-gp120 antibody that is potently and broadly neutralizing. Evolution of affinity of this antibody demonstrates in this case that affinity can be increased while reactivity to variants of human immunodeficiency virus type 1 is broadened. The neutralizing ability of this antibody is improved, as assayed with laboratory and primary clinical isolates of human inmunodeficiency virus type 1. The ability to produce human antibodies of exceptional affinity and broad neutralizing ability has implications for the therapeutic and prophylactic application of antibodies for human immunodeficiency virus type 1 infection.