A universal influenza A vaccine based on the extracellular domain of the M2 protein

Nat Med. 1999 Oct;5(10):1157-63. doi: 10.1038/13484.


The antigenic variation of influenza virus represents a major health problem. However, the extracellular domain of the minor, virus-coded M2 protein is nearly invariant in all influenza A strains. We genetically fused this M2 domain to the hepatitis B virus core (HBc) protein to create fusion gene coding for M2HBc; this gene was efficiently expressed in Escherichia coli. Intraperitoneal or intranasal administration of purified M2HBc particles to mice provided 90-100% protection against a lethal virus challenge. The protection was mediated by antibodies, as it was transferable by serum. The enhanced immunogenicity of the M2 extracellular domain exposed on HBc particles allows broad-spectrum, long-lasting protection against influenza A infections.

MeSH terms

  • Administration, Intranasal
  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / blood
  • Escherichia coli / genetics
  • Hepatitis B Core Antigens / genetics
  • Immunization, Passive
  • Influenza A virus / immunology*
  • Influenza Vaccines / therapeutic use*
  • Injections, Intraperitoneal
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / prevention & control*
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Recombinant Fusion Proteins / immunology
  • Vaccination
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*


  • Antibodies, Viral
  • Hepatitis B Core Antigens
  • Influenza Vaccines
  • M-protein, influenza virus
  • M2 protein, Influenza A virus
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Viral Matrix Proteins