title: Broad humoral and cellular immunity elicited by a bivalent DNA vaccine encoding HA and NP genes from an H5N1 virus.
abstract: Influenza A virus is highly variable and a major viral respiratory pathogen that can cause severe illness in humans. Therefore it is important to induce a sufficient immune response specific to current strains and to heterosubtypic viruses with vaccines. In this study, we developed a dual-promoter-based bivalent DNA vaccine that encodes both hemagglutinin (HA) and nucleoprotein (NP) proteins from a highly pathogenic A/Chicken/Henan/12/2004 (H5N1) virus. Our results show that the expression levels of HA and NP genes from the dual-promoter plasmid are similar to those seen when they are expressed individually in independent plasmids. When the bivalent DNA vaccine was inoculated via intramuscular injection and in vivo electroporation, high levels of both humoral and cellular immune responses were elicited against homologous H5N1 virus and heterosubtypic H9N2 virus. Furthermore, no obvious antigenic competition was observed between HA and NP proteins in the dual-promoter-based bivalent vaccine compared to monovalent vaccines. Our data suggest that a combination of influenza surface and internal viral genes in a dual-promoter-expressing plasmid may provide a new approach for developing a DNA vaccine that may protect not only specifically against a currently circulating strain, but also may cross-protect broadly against new heterosubtypic viruses.
authors.affiliation: Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Zhi-Yang
authors.initials: ZY
authors.lastname: Ling
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Bian
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D049109:Cell Proliferation; D018274:Electroporation; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D010957:Plasmids; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; C109963:hemagglutinin, avian influenza A virus