Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine

Authors


  • Potential conflict of interest: Nothing to report.

  • This study was supported by the Institut Mérieux, the “Hepatibivax” grant from the “Emergence” program of the Agence Nationale pour la Recherche (France), and the FEDER (Fonds Européens de Développements en Region–Région Centre, France) program. The authors thank Dr. Takaji Wakita for the JFH-1 virus strain, Dr. Jens Bukh for the chimeric JFH-1 genomes, S52/JFH1, H77/JFH1, and J4/JFH1, Dr. Charles Rice for the Huh7.5 cell line, Dr. Jonathan Ball for the UKN5.23, UKN 2a1.2, and UKN3A.1.28 plasmids, Dr. Jean Dubuisson for the 7a plasmid and the mAb H52, Dr Harry Greenberg for the mAb A4, Dr. Camille Sureau for the polyclonal anti-HBs Ab, R247, and Dr. Mansun Law for the mAbs, AR3A and AR5A.

Abstract

The development of a prophylactic vaccine against hepatitis C virus (HCV) has become an important medical priority, because 3-4 million new HCV infections are thought to occur each year worldwide. Hepatitis B virus (HBV) is another major human pathogen, but infections with this virus can be prevented with a safe, efficient vaccine, based on the remarkable ability of the envelope protein (S) of this virus to self-assemble into highly immunogenic subviral particles. Chimeric HBV-HCV envelope proteins in which the N-terminal transmembrane domain of S was replaced with the transmembrane domain of the HCV envelope proteins (E1 or E2) were efficiently coassembled with the wild-type HBV S protein into subviral particles. These chimeric particles presented the full-length E1 and E2 proteins from a genotype 1a virus in an appropriate conformation for formation of the E1-E2 heterodimer. Produced in stably transduced Chinese hamster ovary cells and used to immunize New Zealand rabbits, these particles induced a strong specific antibody (Ab) response against the HCV and HBV envelope proteins in immunized animals. Sera containing anti-E1 or anti-E2 Abs elicited by these particles neutralized infections with HCV pseudoparticles and cell-cultured viruses derived from different heterologous 1a, 1b, 2a, and 3 strains. Moreover, the anti–hepatitis B surface response induced by these chimeric particles was equivalent to the response induced by a commercial HBV vaccine. Conclusions: Our results provide support for approaches based on the development of bivalent HBV-HCV prophylactic vaccine candidates potentially able to prevent initial infection with either of these two hepatotropic viruses. (HEPATOLOGY 2013)

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