Preparing for an avian flu pandemic: Method for designing possible subunit vaccines against highly pathogenic avian influenza viruses

A method is described for designing possible subunit vaccines that focus the immune response to the cleavage site of the hemagglutinin molecule of highly pathogenic zoonotic avian influenza viruses. Cleavage of the hemagglutinin is critical to the entry of the virus into target cells. Sequence and three-dimensional structural data are analyzed to map the putative epitopes of antibodies against the hemagglutinin molecule, with particular emphasis on the epitope that includes the cleavage-site of the molecule. The chemical reactivity of the residues outside the cleavage-site epitope is reduced by judicious amino acid replacements so that the resulting molecule would be expected to elicit an immune response predominantly directed at the cleavage site, thereby preventing entry of the virus into target cells. The method is described with emphasis on highly pathogenic zoonotic H5N1 avian influenza viruses; the method could be used also on other avian influenza subtypes.