Hepatitis C virus with a naturally occurring single amino-acid substitution in the E2 envelope protein escapes neutralization by naturally-induced and vaccine-induced antibodies.
Mutations arising in neutralizing epitopes of hepatitis C virus may play a role in the ability of the virus to escape control by neutralizing antibodies and in the establishment of chronic infections. An amino-acid substitution, Q412H, within a major conserved neutralization epitope EP I (aa 412-426) in the E2 glycoprotein is observed in chronic HCV carriers. We found that naturally acquired polyclonal EP I-specific antibodies have an equivalent binding capacity toward either the wild type or the Q412H mutant peptide encompassing the EP I epitope. While EP I-specific antibodies neutralized J6/JFH1 virus in vitro, they did not neutralize J6/JFH1 virus containing the Q412H mutation. Furthermore, we found that plasma obtained from a chimpanzee that had anti-E1/E2 antibodies following experimental immunization, neutralized the wild type J6/JFH1 virus but failed to neutralize the mutant virus. Thus, mutation Q412H found in naturally occurring variants could represent an antibody escape mutation. These data may have important implications for vaccine design.
Duan
Hongying
H
Division of Viral Products, Center for Biologics Evaluation and Research, FDA, 29 Lincoln Drive, Bethesda, MD 20892, USA.
Struble
Evi
E
Zhong
Lilin
L
Mihalik
Kathleen
K
Major
Marian
M
Zhang
Pei
P
Feinstone
Stephen
S
Feigelstock
Dino
D
D019943:Amino Acid Substitution; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D009154:Mutation; D009500:Neutralization Tests; D002679:Pan troglodytes; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus