title: Complete protection against a H5N2 avian influenza virus by a DNA vaccine expressing a fusion protein of H1N1 HA and M2e.
abstract: Most influenza vaccines target hemagglutinin (HA) in order to protect the host against infection. However, theses vaccines are strain-specific due to major antigenic variations of HA. Since it is difficult to predict epidemic and pandemic strains of influenza virus, the development of effective vaccines against divergent influenza viruses is urgently needed. Although M2e-based vaccines are associated with weaker protection than HA-based vaccines that induce neutralizing antibodies against challenge virus matched-strain, the extracellular domain of Matrix 2 protein (M2e) is one of a potential broad-spectrum immunogen because it contains highly conserved sequences among influenza A viruses. In this study, M2e sequence was fused to H1N1 HA DNA (M2e-HA) and the immunogenicity and antiviral efficacy of this DNA vaccine was evaluated in response to challenge with a heterosubtypic H5N2 avian influenza virus. Compared to vaccination with HA or M2e DNA alone, vaccination with M2e-HA DNA or combination of M2e DNA and HA DNA (M2e DNA+HA DNA) induced a broad immunity without evidence of immune interference. In addition, HA-specific CD8(+) and M2e-specific T cell responses elicited by M2e-HA DNA vaccination were significantly higher than those of HA or M2e DNA vaccine alone, respectively. Following challenge with a heterosubtypic influenza virus infection, vaccination with M2e-HA DNA conferred complete protection against mortality. In combination, these results suggest that DNA vaccines expressing a fusion protein, M2e-HA, may provide an attractive approach for the development of broad-spectrum influenza vaccines.
authors.affiliation: Laboratory of Cellular Immunology, Division of Molecular and Life Sciences, POSTECH, Pohang 790-784, Republic of Korea.
authors.forename: Ki Seok
authors.initials: KS
authors.lastname: Park
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Seo
authors.forename: Ji Yeung
authors.initials: JY
authors.lastname: Lee
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Im
authors.forename: Sang Hwan
authors.initials: SH
authors.lastname: Seo
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Song
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Choi
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D053125:Influenza A Virus, H5N2 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012376:Rodent Diseases / Q000276:immunology / Q000517:prevention & control; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins