In vivo and in vitro evidence that cross-reactive antibodies to C-terminus of hypervariable region 1 do not neutralize heterologous hepatitis C virus.
The hypervariable region 1 (HVR1) of hepatitis C virus (HCV) may contain neutralizing epitopes. A chimpanzee in whom cross-reactive anti-HVR1 antibodies had been induced by immunization was challenged with heterologous HCV for clarifying whether cross-reactive anti-HVR1 antibodies can neutralize heterologous HCV. Acute hepatitis C occurred in this chimpanzee after the challenge. Rechallenge with mixtures of the highest titer cross-reactive immune serum and heterologous HCV, after the chimpanzee had cleared the viremia, again resulted in HCV infection. Virus capture assay and inhibition of virus adsorption to susceptible cells, by the immune sera from the chimpanzee and highly cross-reactive monoclonal antibodies (mAbs) against the C-terminus of HVR1 of the challenge virus, showed that cross-reactive anti-HVR1 had no cross-neutralizing activity. The data imply that the HVR1 component is insufficient to develop an effective HCV vaccine.
Esumi
Mariko
M
Department of Pathology, Nihon University School of Medicine, 30-1 Ooyaguchikami-machi, Itabashi-ku, Tokyo 173-8610, Japan. mesumi@med.nihon-u.ac.jp
Zhou
Yi-Hua
YH
Tanoue
Tetsuya
T
Tomoguri
Tetsushi
T
Hayasaka
Ikuo
I
D000208:Acute Disease; D000327:Adsorption; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003429:Cross Reactions; D015195:Drug Design; D000939:Epitopes / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000209:etiology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D002679:Pan troglodytes; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins / Q000276:immunology*; D014766:Viremia / Q000209:etiology
D000911:Antibodies, Monoclonal; D000939:Epitopes; C400562:HVR1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins