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

Xintao Zhang, Ming Liu, Chunguo Liu, Jinling Du, Weilin Shi, Encheng Sun, Hongtao Li, Jianhui Li, Yun Zhang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)290-299
Number of pages10
JournalIntervirology
Volume54
Issue number5
DOIs
StatePublished - Aug 2011

Keywords

  • Avian influenza virus
  • H5N1
  • M2e gene
  • Universal vaccines

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