A universal influenza A vaccine based on the extracellular domain of the M2 protein.
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.
Neirynck
S
S
Department of Molecular Biology, University of Ghent, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
Deroo
T
T
Saelens
X
X
Vanlandschoot
P
P
Jou
W M
WM
Fiers
W
W
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004926:Escherichia coli / Q000235:genetics; D006512:Hepatitis B Core Antigens / Q000235:genetics; D007116:Immunization, Passive; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D006512:Hepatitis B Core Antigens; D007252:Influenza Vaccines; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins