Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies.
Neutralizing antibody responses elicited during infection generally confer protection from infection. Hepatitis C virus (HCV) encodes two glycoproteins E1 and E2 that are essential for virus entry and are the major target for neutralizing antibodies. To assess whether both glycoproteins are required for the generation of a neutralizing antibody response, rodents were immunized with a series of glycoproteins comprising full length and truncated versions. Guinea pigs immunized with HCV-1 genotype 1a E1E2p7, E1E2 or E2 generated high titer anti-glycoprotein antibody responses that neutralized the infectivity of HCVpp and HCVcc expressing gps of the same genotype as the immunizing antigen. Less potent neutralization of viruses bearing the genotype 2 strain J6 gps was observed. In contrast, immunized mice demonstrated reduced anti-gp antibody responses, consistent with their minimal neutralizing activity. Immunization with E2 alone was sufficient to induce a high titer response that neutralized HCV pseudoparticles (HCVpp) bearing diverse glycoproteins and cell culture grown HCV (HCVcc). The neutralization titer was reduced 3-fold by the presence of lipoproteins in human sera. Cross-competition of the guinea pig anti-E1E2 immune sera with a panel of epitope mapped anti-E2 monoclonal antibodies for binding E2 identified a series of epitopes within the N-terminal domain that may be immunogenic in the immunized rodents. These data demonstrate that recombinant E2 and E1E2 can induce polyclonal antibody responses with cross-reactive neutralizing activity, supporting the future development of prophylactic and therapeutic vaccines.
Stamataki
Zania
Z
University of Birmingham, Division of Immunity and Infection, Birmingham, UK.
Coates
Stephen
S
Evans
Matthew J
MJ
Wininger
Mark
M
Crawford
Kevin
K
Dong
Christine
C
Fong
Yiu-Lian
YL
Chien
David
D
Abrignani
Sergio
S
Balfe
Peter
P
Rice
Charles M
CM
McKeating
Jane A
JA
Houghton
Michael
M
D000818:Animals; D018929:Cell Culture Techniques; D003429:Cross Reactions; D005838:Genotype; D016174:Hepacivirus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D009500:Neutralization Tests; D012377:Rodentia; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus