Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice

被引:8
作者
Bazhan, Sergei [1 ]
Antonets, Denis [1 ]
Starostina, Ekaterina [2 ]
Ilyicheva, Tatyana [3 ]
Kaplina, Olga [2 ]
Marchenko, Vasiliy [3 ]
Durymanov, Alexander [3 ]
Oreshkova, Svetlana [2 ]
Karpenko, Larisa [2 ]
机构
[1] State Res Ctr Virol & Biotechnol Vector, Dept Theoret, Koltsov 630559, Novosibirsk Reg, Russia
[2] State Res Ctr Virol & Biotechnol Vector, Bioengn Dept, Koltsov 630559, Novosibirsk Reg, Russia
[3] State Res Ctr Virol & Biotechnol Vector, Dept Zoonot Infect & Influenza, Koltsov 630559, Novosibirsk Reg, Russia
关键词
influenza virus; DNA-vaccine constructs; artificial polyepitope T-cell immunogens; hemagglutinin stem region; M2; protein; cross-protective influenza immunity; T-CELLS; IMMUNITY; ELECTROPORATION; NANOPARTICLES; ANTIBODIES; VIRUSES;
D O I
10.3390/vaccines8030448
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页码:1 / 17
页数:17
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