A "universal" human influenza A vaccine.
We have previously reported on a universal human influenza A vaccine, based on the external domain of the transmembrane viral M2-protein (M2e) [Nature Medicine 5 (1999) 1119]. M2-protein is scarcely present on the virus but is abundantly expressed on virus-infected cells. The external domain, M2e, is 23-amino acids long and as such weakly immunogenic. But when presented on an appropriate carrier, such as hepatitis B virus core (HBc) particles, it induces a high titer antibody response that in mice effectively protects against a potentially lethal influenza infection. The advantage of M2e as an antigen is the conservation of its sequence that has hardly changed since the first influenza virus was isolated in 1933, despite numerous epidemics and several pandemics. Various constructs, e.g. M2e fused at the N-terminus of the HBc subunit or inserted in the immuno-dominant loop, were evaluated as a vaccine. They conferred full protection when administered together with an adjuvant. Several adjuvants were tested in conjunction with intraperitoneal vaccine administration, while the non-toxic enterotoxin mutant LT(R192G) was used for intranasal vaccination. Appropriate combinations of vaccine construct and adjuvant allowed to obtain anti-M2e IgG2a serum titers above 10,000, and this provided complete protection.
Fiers
W
W
Laboratory Molecular Biology, University Ghent & VIB, Ledeganckstreet 35, 9000 Ghent, Belgium. fiers@dmb.rug.ac.be
De Filette
M
M
Birkett
A
A
Neirynck
S
S
Min Jou
W
W
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000086082:Viroporin Proteins
D006512:Hepatitis B Core Antigens; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins