Identification and Characterization of Broadly Neutralizing Human Monoclonal Antibodies Directed against the E2 Envelope Glycoprotein of Hepatitis C Virus

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Published in:	Journal of Virology Vol. 83; no. 23; pp. 12473 - 12482
Main Authors:	BROERING, Teresa J, GARRITY, Kerry A, BOATRIGHT, Naomi K, SLOAN, Susan E, SANDOR, Frantisek, THOMAS, William D, SZABO, Gyongyi, FINBERG, Robert W, AMBROSINO, Donna M, BABCOCK, Gregory J
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for Microbiology 01-12-2009 American Society for Microbiology (ASM)
Subjects:	Amino Acid Sequence Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - isolation & purification Biological and medical sciences Conserved Sequence Epitope Mapping Epitopes, B-Lymphocyte - genetics Epitopes, B-Lymphocyte - immunology Fundamental and applied biological sciences. Psychology Hepacivirus - immunology Hepatitis C Antibodies - immunology Hepatitis C Antibodies - isolation & purification Humans Mice Mice, Transgenic Microbiology Miscellaneous Molecular Sequence Data Neutralization Tests Vaccines and Antiviral Agents Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Viral Envelope Proteins - immunology Virology Virus Human Envelope virus Glycoprotein Identification Monoclonal antibody Flaviviridae Hepatitis C virus Hepacivirus Neutralizing antibody
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Abstract	Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI
AbstractList	Nearly all livers transplanted into hepatitis C virus (HCV)-positive patients become infected with HCV, and 10 to 25% of reinfected livers develop cirrhosis within 5 years. Neutralizing monoclonal antibody could be an effective therapy for the prevention of infection in a transplant setting. To pursue this treatment modality, we developed human monoclonal antibodies (HuMAbs) directed against the HCV E2 envelope glycoprotein and assessed the capacity of these HuMAbs to neutralize a broad panel of HCV genotypes. HuMAb antibodies were generated by immunizing transgenic mice containing human antibody genes (HuMAb mice; Medarex Inc.) with soluble E2 envelope glycoprotein derived from a genotype 1a virus (H77). Two HuMAbs, HCV1 and 95-2, were selected for further study based on initial cross-reactivity with soluble E2 glycoproteins derived from genotypes 1a and 1b, as well as neutralization of lentivirus pseudotyped with HCV 1a and 1b envelope glycoproteins. Additionally, HuMAbs HCV1 and 95-2 potently neutralized pseudoviruses from all genotypes tested (1a, 1b, 2b, 3a, and 4a). Epitope mapping with mammalian and bacterially expressed proteins, as well as synthetic peptides, revealed that HuMAbs HCV1 and 95-2 recognize a highly conserved linear epitope spanning amino acids 412 to 423 of the E2 glycoprotein. The capacity to recognize and neutralize a broad range of genotypes, the highly conserved E2 epitope, and the fully human nature of the antibodies make HuMAbs HCV1 and 95-2 excellent candidates for treatment of HCV-positive individuals undergoing liver transplantation. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI
Author	Robert W. Finberg Gregory J. Babcock Naomi K. Boatright Frantisek Sandor Susan E. Sloan Teresa J. Broering Kerry A. Garrity William D. Thomas Jr Donna M. Ambrosino Gyongyi Szabo
AuthorAffiliation	MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, 1 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 2
AuthorAffiliation_xml	– name: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, 1 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 2
Author_xml	– sequence: 1 givenname: Teresa J surname: BROERING fullname: BROERING, Teresa J organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States – sequence: 2 givenname: Kerry A surname: GARRITY fullname: GARRITY, Kerry A organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States – sequence: 3 givenname: Naomi K surname: BOATRIGHT fullname: BOATRIGHT, Naomi K organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States – sequence: 4 givenname: Susan E surname: SLOAN fullname: SLOAN, Susan E organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States – sequence: 5 givenname: Frantisek surname: SANDOR fullname: SANDOR, Frantisek organization: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States – sequence: 6 givenname: William D surname: THOMAS fullname: THOMAS, William D organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States – sequence: 7 givenname: Gyongyi surname: SZABO fullname: SZABO, Gyongyi organization: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States – sequence: 8 givenname: Robert W surname: FINBERG fullname: FINBERG, Robert W organization: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States – sequence: 9 givenname: Donna M surname: AMBROSINO fullname: AMBROSINO, Donna M organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States – sequence: 10 givenname: Gregory J surname: BABCOCK fullname: BABCOCK, Gregory J organization: MassBiologics, University of Massachusetts Medical School, Boston, Massachusetts, United States
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Keywords	Virus Human Envelope virus Glycoprotein Identification Monoclonal antibody Flaviviridae Hepatitis C virus Hepacivirus Neutralizing antibody
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Snippet	Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley... Nearly all livers transplanted into hepatitis C virus (HCV)-positive patients become infected with HCV, and 10 to 25% of reinfected livers develop cirrhosis...
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StartPage	12473
SubjectTerms	Amino Acid Sequence Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - isolation & purification Biological and medical sciences Conserved Sequence Epitope Mapping Epitopes, B-Lymphocyte - genetics Epitopes, B-Lymphocyte - immunology Fundamental and applied biological sciences. Psychology Hepacivirus - immunology Hepatitis C Antibodies - immunology Hepatitis C Antibodies - isolation & purification Humans Mice Mice, Transgenic Microbiology Miscellaneous Molecular Sequence Data Neutralization Tests Vaccines and Antiviral Agents Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Viral Envelope Proteins - immunology Virology
Title	Identification and Characterization of Broadly Neutralizing Human Monoclonal Antibodies Directed against the E2 Envelope Glycoprotein of Hepatitis C Virus
URI	http://jvi.asm.org/content/83/23/12473.abstract https://www.ncbi.nlm.nih.gov/pubmed/19759151 https://search.proquest.com/docview/733131195 https://pubmed.ncbi.nlm.nih.gov/PMC2786766
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