Soluble recombinant influenza vaccines.
Soluble, recombinant forms of influenza A virus haemagglutinin and neuraminidase have been produced in cells of lower eukaryotes, and shown in a mouse model to induce complete protective immunity against a lethal virus challenge. Soluble neuraminidase, produced in a baculovirus system, consisted of tetramers, dimers and monomers. Only the tetramers were enzymatically active. The immunogenicity decreased very considerably in the order tetra > di > mono. Therefore, we fused the head part of the neuraminidase gene to a tetramerizing leucine zipper sequence; the resulting product was enzymatically active, tetrameric neuraminidase. The protective immunity induced by this engineered neuraminidase, however, remained fairly strain-specific. A third influenza A virus protein, the M2 protein, has only 23 amino acids exposed on the outer membrane surface. This extracellular part, M2e, has been remarkably conserved in all human influenza A strains since 1933. By fusing the M2e sequence to hepatitis B virus core protein, we could obtain highly immunogenic particles that induced complete, strain-independent, long-lasting protection in mice against a lethal viral challenge. Native M2 is a tetrameric protein and this conformation of the M2e part can also be mimicked by fusing this sequence to a tetramerizing leucine zipper. The potential of the resulting protein as a vaccine candidate remains to be evaluated.
Fiers
W
W
Laboratory of Molecular Biology, University of Ghent and Flanders Interuniversity Institute for Biotechnology, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium. fiers@dmb.rug.ac.be
Neirynck
S
S
Deroo
T
T
Saelens
X
X
Jou
W M
WM
D000595:Amino Acid Sequence; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics; D009980:Influenza A virus; D007252:Influenza Vaccines / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D009439:Neuraminidase; D012995:Solubility; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics; D000086082:Viroporin Proteins
D007252:Influenza Vaccines; D009439:Neuraminidase; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins