title: Vaccination with different M2e epitope densities confers partial protection against H5N1 influenza A virus challenge in chickens.
abstract: OBJECTIVE
  Currently, research is focused on universal influenza vaccines based on various ectodomains of the influenza matrix protein 2 (M2e). Such vaccines are tested mostly using mouse-adapted influenza viruses and in mouse or ferret models. The aim of this study was to investigate in a chicken model the protective efficacy of vaccines based on avian-type M2e at different epitope densities.
  
  
  METHODS
  On the basis of the optimized avian-type M2e gene, recombinant plasmids that contained tandem copies of different M2e were constructed and expressed in Escherichia coli. The expression and immunogenicity of the proteins were confirmed by SDS-PAGE and Western blot, as well as immunofluorescence assay and enzyme-linked immunosorbent assay. Animals were immunized with fusion proteins emulsified with an appropriate adjuvant and then infected with highly pathogenic influenza virus of A/chicken/Guangdong/04 (H5N1). Antibody levels, survival rate and weight loss were investigated.
  
  
  RESULTS
  Multiple copies of M2e were highly expressed; higher epitope density engendered better protection but there was not a linear increase. Among the fusion proteins, the MBP-3·M2e fusion protein showed the best protective efficacy.
  
  
  CONCLUSIONS
  This study has provided evidence that the immune response to avian-type M2e-based subunit vaccines was greater in chickens than that in mice. In addition, higher M2e epitope density can yield better protection, but not in a linear fashion.
authors.affiliation: Animal Influenza Laboratory of the Ministry of Agriculture, and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, PR China.
authors.forename: Xintao
authors.initials: X
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Chunguo
authors.initials: C
authors.lastname: Liu
authors.forename: Jinling
authors.initials: J
authors.lastname: Du
authors.forename: Weilin
authors.initials: W
authors.lastname: Shi
authors.forename: Encheng
authors.initials: E
authors.lastname: Sun
authors.forename: Hongtao
authors.initials: H
authors.lastname: Li
authors.forename: Jianhui
authors.initials: J
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002645:Chickens; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins