Vaccination with different M2e epitope densities confers partial protection against H5N1 influenza A virus challenge in chickens

Intervirology. 2011;54(5):290-9. doi: 10.1159/000319440. Epub 2011 Jan 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Viral / blood
  • Chickens
  • Disease Models, Animal
  • Epitopes / genetics
  • Epitopes / immunology*
  • Immunoglobulin G / blood
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Influenza in Birds / immunology
  • Influenza in Birds / prevention & control
  • Survival Analysis
  • Vaccination / methods*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Epitopes
  • Immunoglobulin G
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Vaccines, Synthetic
  • Viral Matrix Proteins