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Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies.

Stamataki, Zania and Coates, Stephen and Evans, Matthew J and Wininger, Mark and Crawford, Kevin and Dong, Christine and Fong, Yiu-Lian and Chien, David and Abrignani, Sergio and Balfe, Peter and Rice, Charles M and McKeating, Jane A and Houghton, Michael (2007) Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies. Vaccine, 25 (45). pp. 7773-84. ISSN 0264-410X

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Identification Number/DOI: http://dx.doi.org/10.1016/j.vaccine.2007.08.053

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.

Type of Work:Article
Date:2007 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Medicine
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:Elsevier Ltd.
ID Code:481
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