In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity
| Autor: | Carlos F. Barbas, R. M. Hendry, Peter L. Nara, Lynette S. W. Sawyer, Dana Hu, Dennis R. Burton, Doug Cababa, N Dunlop |
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| Rok vydání: | 1994 |
| Předmět: |
HIV Antigens
Molecular Sequence Data Antibody Affinity Complementarity determining region Cross Reactions HIV Antibodies HIV Envelope Protein gp120 In Vitro Techniques medicine.disease_cause Cross-reactivity Virus Structure-Activity Relationship Antigen Neutralization Tests medicine Humans Amino Acid Sequence Binding site Multidisciplinary Binding Sites biology Base Sequence Virology biology.protein HIV-1 Mutagenesis Site-Directed Binding Sites Antibody Antibody Systematic evolution of ligands by exponential enrichment Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 91(9) |
| ISSN: | 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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