Antiviral Res. 2017 Jun 27. pii: S0166-3542(17)30219-X. doi: 10.1016/j.antiviral.2017.06.017. [Epub ahead of print]
A novel chimeric Hepatitis B virus S/preS1 antigen produced in mammalian and plant cells elicits stronger humoral and cellular immune response than the standard vaccine-constituent, S protein.Dobrica MO1, Lazar C1, Paruch L2, Skomedal H2, Steen H2, Haugslien S2, Tucureanu C3, Caras I3, Onu A3, Ciulean S3, Branzan A4, Clarke JL5, Stavaru C6, Branza-Nichita N7. Author information 1Institute of Biochemistry of the Romanian Academy, Bucharest, Romania.2NIBIO - Norwegian Institute for Bioeconomy Research, Ås, Norway.3"Cantacuzino" National Research Institute, Bucharest, Romania.4Institute of Biology of the Romanian Academy, Bucharest, Romania.5NIBIO - Norwegian Institute for Bioeconomy Research, Ås, Norway. Electronic address: [email protected].6"Cantacuzino" National Research Institute, Bucharest, Romania. Electronic address: [email protected].7Institute of Biochemistry of the Romanian Academy, Bucharest, Romania. Electronic address: [email protected].
AbstractChronic Hepatitis B Virus (HBV) infection leads to severe liver pathogenesis associated with significant morbidity and mortality. As no curable medication is yet available, vaccination remains the most cost-effective approach to limit HBV spreading and control the infection. Although safe and efficient, the standard vaccine based on production of the small (S) envelope protein in yeast fails to elicit an effective immune response in about 10% of vaccinated individuals, which are at risk of infection. One strategy to address this issue is the development of more immunogenic antigens. Here we describe a novel HBV antigen obtained by combining relevant immunogenic determinants of S and large (L) envelope proteins. Our approach was based on the insertion of residues 21-47 of the preS1 domain of the L protein (nomenclature according to genotype D), involved in virus attachment to hepatocytes, within the external antigenic loop of S. The resulting S/preS121-47 chimera was successfully produced in HEK293T and Nicotiana benthamiana plants, as a more economical recombinant protein production platform. Comparative biochemical, functional and electron microscopy analysis indicated assembly of the novel antigen into subviral particles in mammalian and plant cells. Importantly, these particles preserve both S- and preS1-specific epitopes and elicit significantly stronger humoral and cellular immune responses than the S protein, in both expression systems used. Our data promote this antigen as a promising vaccine candidate to overcome poor responsiveness to the conventional, S protein-based, HBV vaccine.
发表于 2017-7-3 18:13