Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

Antiviral Res. 2013 Sep;99(3):328-35. doi: 10.1016/j.antiviral.2013.06.010. Epub 2013 Jun 27.

Abstract

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

Keywords: Cross protection; M2e VLPs; M2e cross-reactivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Cross Reactions
  • Female
  • Humans
  • Immunity*
  • Immunization
  • Influenza A virus / chemistry
  • Influenza A virus / genetics
  • Influenza A virus / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology
  • Influenza, Human / immunology*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Protein Structure, Tertiary
  • Viral Matrix Proteins / administration & dosage
  • Viral Matrix Proteins / chemistry*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Viral Matrix Proteins