人免疫缺陷病毒1型中和性人抗体的体外进化，以增强亲和力并拓宽毒株交叉反应性。
In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity.
作者信息
Barbas C F, Hu D, Dunlop N, Sawyer L, Cababa D, Hendry R M, Nara P L, Burton D R
机构信息
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
出版信息
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3809-13. doi: 10.1073/pnas.91.9.3809.
Abstract
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 immunodeficiency 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.
摘要
本文描述了一种可提高抗体亲和力的方法。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。互补决定区是随机诱变的目标，随后通过噬菌体展示方法选择适应性，在这种情况下是增加结合亲和力。当前的研究针对一种能有效且广泛中和的人CD4结合位点抗gp120抗体。在这种情况下，该抗体亲和力的进化表明，在增加亲和力的同时，对1型人类免疫缺陷病毒变体的反应性也会拓宽。用1型人类免疫缺陷病毒的实验室和原代临床分离株进行检测，该抗体的中和能力得到了提高。产生具有卓越亲和力和广泛中和能力的人抗体的能力对1型人类免疫缺陷病毒感染的抗体治疗和预防应用具有重要意义。
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