title: The highly conserved HA2 protein of the influenza A virus induces a cross protective immune response.
abstract: Existing influenza vaccines protect mostly homologous subtypes and acted most effectively only when well matched to the circulating strain. Immunization with an updated vaccine is therefore necessary to maintain long-term protection and the development of a broadly protective influenza vaccine against the threat of pandemic outbreak. The highly conserved HA2 glyco-polypeptide (HA2 gp) is a promising new candidate for such an influenza vaccine. Helical domain and the fusion peptide (residues 15-137) of surface antigen from influenza A subtype A/EM/Korea/W149/06 (H5N1) was used to assess the potentiality of HA2 vaccination against multiple subtypes of the influenza viruses. The construct, named H5HA2 was expressed in Escherichia coli and allowed to refold from inclusion bodies. Purified proteins were used to investigate the immunogenicity of H5HA2 and its potential for cross protection. The immunization of mice with H5HA2 induced HA2 antibodies, HA2 specific T-cell responses, and protection against homologous A/EM/Korea/W149/06 (H5N1) influenza. Immunized mice were also protected from two distinct heterosubtypes of influenza: A/Puerto Rico/1/34(H1N1) and bird/Korea/w81/2005(H5N2). Results suggest that recombinant proteins based on the highly conserved residues within HA2 are candidates for the development of vaccines against pandemic outbreaks of emergent influenza variants.
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Mohammed Y E
authors.initials: MY
authors.lastname: Chowdhury
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Moon
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Choi
authors.forename: Melbourne R
authors.initials: MR
authors.lastname: Talactac
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Min-Eun
authors.initials: ME
authors.lastname: Park
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Son
authors.forename: Kwang-Soon
authors.initials: KS
authors.lastname: Shin
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D053125:Influenza A Virus, H5N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C109963:hemagglutinin, avian influenza A virus
keywords: 50% mouse lethal dose; BSL; Cross protection; ELISA; ELISPOT; HA2; HRP; Hemagglutinin; IgG; Immunization; Influenza vaccine; MLD(50); OD; TCID(50); bio-safety level; day post infection; dpi; enzyme-linked immunosorbent assay; enzyme-linked immunosorbent spot; glycol-polypeptide; gp; hemagglutinin-2; horseradish peroxidase; immunoglobulin G; median tissue culture infectious dose; optical density