In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity
Carlos F. Barbas,Dana Hu,N Dunlop,Lynette S. W. Sawyer,Doug Cababa,R. M. Hendry,Peter L. Nara,Dennis R. Burton +7 more
Reads0
Chats0
TLDR
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.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.read more
Citations
More filters
Journal ArticleDOI
Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen.
Yongmei Chen,Christian Wiesmann,Germaine Fuh,Bing Li,H.W. Christinger,P. Mckay,A.M. de Vos,Henry B. Lowman +7 more
TL;DR: The final antibody has improved affinity for several VEGF variants as compared with the parental antibody; however, some contact residues on V EGF differ in their contribution to the energetics of Fab binding.
Journal ArticleDOI
Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody
Dennis R. Burton,Jayashree Pyati,Raju Koduri,Stephen J. Sharp,George B. Thornton,Paul W. H. I. Parren,Lynette S. W. Sawyer,R. Michael Hendry,N Dunlop,Peter L. Nara,Michael Lamacchia,Eileen Garratty,E. Richard Stiehm,Yvonne J. Bryson,Yunzhen Cao,John P. Moore,David D. Ho,Carlos F. Barbas +17 more
TL;DR: A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization, implying the conservation of a structural feature on gp120, which could be important in vaccine design.
Patent
Dual variable domain immunoglobulins and uses thereof
TL;DR: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.
Journal ArticleDOI
CDR Walking Mutagenesis for the Affinity Maturation of a Potent Human Anti-HIV-1 Antibody into the Picomolar Range
Wei-Ping Yang,Kimberly Green,Sally Pinz-Sweeney,Amelia T. Briones,Dennis R. Burton,Carlos F. Barbas +5 more
TL;DR: The methodology presented here provides a route for the improvement of the affinities of antibodies typical of tertiary immune responses into the picomolar range and may have profound effects on the utility of antibodies as therapeutic and prophylactic agents.
Patent
Humanization of murine antibody
Carlos F. Barbas,Christoph Rader +1 more
TL;DR: In this article, the amino acid sequences of a light chain complementarity determining region from a mouse antibody are grafted onto a human light chain, and a heavy chain complementary determining region is grafted on a human antibody heavy chain to produce libraries from which a humanized murine antibody having the desired specificity is selected.