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a weak neutralizing antibody response to hepatitis c virus envelope glycoprotein enhances virus infection疲软的中和抗体反应丙型肝炎病毒包膜糖蛋白提高病毒感染
A Weak Neutralizing Antibody Response to Hepatitis C
Virus Envelope Glycoprotein Enhances Virus Infection
1 1 1 1,2 1,2
Keith Meyer , Arup Banerjee , Sharon E. Frey , Robert B. Belshe , Ranjit Ray *
1 Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, United States of America, 2 Molecular Microbiology Immunology, Saint Louis University, St.
Louis, Missouri, United States of America
Abstract
We have completed a phase 1 safety and immunogenicity trial with hepatitis C virus (HCV) envelope glycoproteins, E1 and
E2, with MF59 adjuvant as a candidate vaccine. Neutralizing activity to HCV genotype 1a was detected in approximately
25% of the vaccinee sera. In this study, we evaluated vaccinee sera from poor responders as a potential source of antibody
dependent enhancement (ADE) of HCV infection. Sera with poor neutralizing activity enhanced cell culture grown HCV
genotype 1a or 2a, and surrogate VSV/HCV pseudotype infection titer, in a dilution dependent manner. Surrogate
pseudotypes generated from individual HCV glycoproteins suggested that antibody to the E2 glycoprotein; but not the E1
glycoprotein, was the principle target for enhancing infection. Antibody specific to FcRII expressed on the hepatic cell
surface or to the Fc portion of Ig blocked enhancement of HCV infection by vaccinee sera. Together, the results from in vitro
studies suggested that enhancement of viral infectivity may occur in the absence of a strong antibody response to HCV
envelope glycoproteins.
Citation: Meyer K, Banerjee A, Frey SE, Belshe RB, Ray R (2011) A Weak Neutralizing Antibody Response to Hepatitis C Virus Envelope Glycoprotein Enhances Virus
Infecti
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