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Oxford University Press (OUP), The Journal of Infectious Diseases, 6(204), p. 837-844

DOI: 10.1093/infdis/jir423

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Clearance of Genotype 1b Hepatitis C Virus in Chimpanzees in the Presence of Vaccine-Induced E1-Neutralizing Antibodies

Journal article published in 2011 by Erik Depla, Babs E. (Babs) Verstrepen ORCID, Christine S. (Christine S.) Rollier, Gwenny Mares, Joost A. R. (Joost A. R.) Drexhage, Sofie Priem, Ernst J. (Ernst) Verschoor, Christelle Granier, Gerrit Koopman, Marlène Dreux, François L. (Francxois L.) Cosset ORCID, Geert Maertens, Jonathan L. (Jonathan) Heeney
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Accumulating evidence indicates that neutralizing antibodies play an important role in protection from chronic hepatitis C virus (HCV) infection. Efforts to elicit such responses by immunization with intact heterodimeric E1E2 envelope proteins have met with limited success. To determine whether antigenic sites, which are not exposed by the combined E1E2 heterodimer structure, are capable of eliciting neutralizing antibody responses, we expressed and purified each as separate recombinant proteins E1 and E2, from which the immunodominant hypervariable region (HVR-1) was deleted. Immunization of chimpanzees with either E1 or E2 alone induced antigen-specific T-helper cytokines of similar magnitude. Unexpectedly, the capacity to neutralize HCV was observed in E1 but not in animals immunized with E2 devoid of HVR-1. Furthermore, in vivo only E1-vaccinated animals exposed to the heterologous HCV-1b inoculum cleared HCV infection.