Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1

Science

Volumn 329, Issue 5993, 2010, Pages 856-861

  Wu, Xueling ^a   Yang, Zhi Yong ^a   Li, Yuxing ^a   Hogerkorp, Carl Magnus ^a,d   Schief, William R ^b   Seaman, Michael S ^c   Zhou, Tongqing ^a   Schmidt, Stephen D ^a   Wu, Lan ^a   Xu, Ling ^a   Longo, Nancy S ^a   McKee, Krisha ^a   O'Dell, Sijy ^a   Louder, Mark K ^a   Wycuff, Diane L ^a   Feng, Yu ^a,e   Nason, Martha ^a   Doria Rose, Nicole ^a   Connors, Mark ^a   Kwong, Peter D ^a   Roederer, Mario ^a   Wyatt, Richard T ^a,e   Nabel, Gary J ^a   Mascola, John R ^a   more..

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d NOVO NORDISK A S   (Denmark)

^e SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; GLYCOPROTEIN; HUMAN MONOCLONAL ANTIBODY; IMMUNOGLOBULIN G;

ANTIBODY; ANTIGEN; CLONAL ORGANISM; CONSERVATION GENETICS; DESIGN; GENE EXPRESSION; HUMAN IMMUNODEFICIENCY VIRUS; IDENTIFICATION KEY; INFECTIOUS DISEASE; NEUTRALIZATION; PROTEIN; VACCINE;

ANTIGENICITY; ARTICLE; B LYMPHOCYTE; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOGLOBULIN GENE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR BINDING; VIRUS ENVELOPE; VIRUS NEUTRALIZATION;

AIDS VACCINES; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ANTIBODY SPECIFICITY; ANTIGENS, CD4; B-LYMPHOCYTES; BINDING SITES, ANTIBODY; CROSS REACTIONS; DRUG DESIGN; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITOPES; GENES, IMMUNOGLOBULIN HEAVY CHAIN; GENES, IMMUNOGLOBULIN LIGHT CHAIN; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; NEUTRALIZATION TESTS; PROTEIN ENGINEERING; RECOMBINANT PROTEINS;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77954920017     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1187659     Document Type: Article

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39. This research was supported by the Intramural Research Program of the Vaccine Research Center, the Division of Clinical Research and the Laboratory of Immunoregulation of National Institute of Allergy and Infectious Diseases, NIH. M.S.S. was supported in part by the Bill and Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery, Comprehensive Antibody-Vaccine Immune Monitoring Consortium, grant number 38619. W.R.S. was supported by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery through a grant to Seattle Biomedical Research Institute and by the International AIDS Vaccine Initiative. Nucleotide sequences of VRC01, VRC02, and VRC03 variable regions are available under GenBank accession numbers GU980702 to GU980707. Patent applications have been filed by the NIH on mAbs VRC01, VRC02, and VRC03 (listed investigators are X.W., Z.Y.Y., Y.L., C.M.H, W.R.S., T.Z., M.C., P.D.K., M.R., R.T.W., G.J.N., and J.R.M.) and on the RSC3 probe (listed investigators are Z.Y.Y., W.R.S., T.Z., P.D.K. and G.J.N.). We thank M. Nussenzweig and J. Scheid (Laboratory of Molecular Immunology, Howard Hughes Medical Institute, Rockefeller University, New York, NY) for sharing expertise and reagents for IgG cloning and expression; B. Haynes (Duke University Medical Center, Durham, NC) for sharing reagents and PCR methods; S. Perfetto, R. Nguyen, and D. Ambrozak for assistance with cell sorting; E. Lybarger for neutralization assays; J. Stuckey and B. Hartman for assistance with figures; A. Tislerics for manuscript preparation; D. Follman for statistical advice; C. Carrico for discussions on resurfacing; Y.-E. A. Ban and L. Kong for glycan modeling; P. Chattopadhyay and J. Yu for fluorescent antibody production and qualification; C. Williamson (University of Capetown, Capetown, South Africa), M. Thomson (Instituto de Salud Carlos III, Madrid, Spain), J. Overbaugh (Fred Hutchinson Cancer Research Center, Seattle, WA), and S. Tovanabutra and E. Sanders-Buell (Henry M. Jackson Foundation and the U.S. Military HIV Research Program, Rockville, MD) for contributing HIV-1 Env plasmids for pseudovirus production.