Definition of a conserved immunodominant domain on hepatitis C virus E2 glycoprotein by neutralizing human monoclonal antibodies.
Development of a successful hepatitis C virus (HCV) vaccine requires the definition of neutralization epitopes that are conserved among different HCV genotypes. Five human monoclonal antibodies (HMAbs) are described that cross-compete with other antibodies to a cluster of overlapping epitopes, previously designated domain B. Each HMAb broadly neutralizes retroviral pseudotype particles expressing HCV E1 and E2 glycoproteins, as well as the infectious chimeric genotype 1a and genotype 2a viruses. Alanine substitutions of residues within a region of E2 involved in binding to CD81 showed that critical E2 contact residues involved in the binding of representative antibodies are identical to those involved in the binding of E2 to CD81.
Keck
Zhen-Yong
ZY
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Li
Ta-Kai
TK
Xia
Jinming
J
Gal-Tanamy
Meital
M
Olson
Oakley
O
Li
Sophia H
SH
Patel
Arvind H
AH
Ball
Jonathan K
JK
Lemon
Stanley M
SM
Foung
Steven K H
SK
D000409:Alanine / Q000378:metabolism; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018937:Hepatitis C Antibodies; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D000409:Alanine