Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
Sergei Bazhan,
Denis Antonets,
Ekaterina Starostina,
Tatyana Ilyicheva,
Olga Kaplina,
Vasiliy Marchenko,
Alexander Durymanov,
Svetlana Oreshkova,
Larisa Karpenko
Affiliations
Sergei Bazhan
Theoretical Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Denis Antonets
Theoretical Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Ekaterina Starostina
Bioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Tatyana Ilyicheva
Department of Zoonotic Infections and Influenza, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Olga Kaplina
Bioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Vasiliy Marchenko
Department of Zoonotic Infections and Influenza, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Alexander Durymanov
Department of Zoonotic Infections and Influenza, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Svetlana Oreshkova
Bioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Larisa Karpenko
Bioengineering Department, State Research Center of Virology and Biotechnology “Vector”, Koltsovo 630559, Novosibirsk Region, Russia
Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated response, since they contain conservative epitopes capable to induce antibodies and cytotoxic T lymphocytes (CTLs) to a wide range of influenza virus subtypes. Methods: In this study, we generated DNA vaccine constructs encoding artificial antigens AgH1, AgH3, and AgM2 designed on the basis of conservative hemagglutinin stem fragments of two influenza A virus subtypes, H1N1 and H3N2, and conservative M2 protein, and evaluate their immunogenicity and protective efficacy. To obtain DNA vaccine constructs, genes encoding the designed antigens were cloned into a pcDNA3.1 vector. Expression of the target genes in 293T cells transfected with DNA vaccine constructs has been confirmed by synthesis of specific mRNA. Results: Immunization of BALB/c mice with DNA vaccines encoding these antigens was shown to evoke humoral and T-cell immune responses as well as a moderated statistically significant cross-protective effect against two heterologous viruses A/California/4/2009 (H1N1pdm09) and A/Aichi/2/68 (H3N2). Conclusions: The results demonstrate a potential approach to creating a universal influenza vaccine based on artificial antigens.
