Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus
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Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. / Giang, Erick; Dorner, Marcus; Prentoe, Jannick C; Dreux, Marlène; Evans, Matthew J; Bukh, Jens; Rice, Charles M; Ploss, Alexander; Burton, Dennis R; Law, Mansun.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 16, 17.04.2012, p. 6205-10.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus
AU - Giang, Erick
AU - Dorner, Marcus
AU - Prentoe, Jannick C
AU - Dreux, Marlène
AU - Evans, Matthew J
AU - Bukh, Jens
AU - Rice, Charles M
AU - Ploss, Alexander
AU - Burton, Dennis R
AU - Law, Mansun
PY - 2012/4/17
Y1 - 2012/4/17
N2 - Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.
AB - Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV.
KW - Amino Acid Sequence
KW - Animals
KW - Antibodies, Monoclonal
KW - Antibodies, Neutralizing
KW - Antibody Specificity
KW - Antigens, CD81
KW - Cell Line, Tumor
KW - Enzyme-Linked Immunosorbent Assay
KW - Epitopes, B-Lymphocyte
KW - Genotype
KW - HEK293 Cells
KW - Hepacivirus
KW - Hepatitis C
KW - Hepatitis C Antibodies
KW - Humans
KW - Immunoblotting
KW - Mice
KW - Molecular Sequence Data
KW - Peptide Library
KW - Viral Envelope Proteins
KW - Viral Hepatitis Vaccines
U2 - 10.1073/pnas.1114927109
DO - 10.1073/pnas.1114927109
M3 - Journal article
C2 - 22492964
VL - 109
SP - 6205
EP - 6210
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 16
ER -
ID: 131072702