title: An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.
abstract: In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Ho-Chuen
authors.initials: HC
authors.lastname: Leung
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Chris Chung-Sing
authors.initials: CC
authors.lastname: Chan
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Vincent Kwok-Man
authors.initials: VK
authors.lastname: Poon
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Han-Jun
authors.initials: HJ
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Chung-Yan
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Fai
authors.initials: F
authors.lastname: Ng
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Huang
authors.affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
mesh_terms: D000482:Allantois; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D002645:Chickens; D056738:Cross Protection; D003429:Cross Reactions; D004285:Dogs; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008168:Lung / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D013047:Specific Pathogen-Free Organisms; D022223:Vaccines, Subunit / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins
keywords: H7N9; M2e; cross protection; influenza A virus; peptide vaccine