title: An avian influenza vaccine for humans targeting the polymerase B2 protein inside the capsid instead of hemagglutinin or neuramidase on the virus surface.
abstract: Vaccines for avian influenza typically are aimed at hemagglutinin or neuramidase on the outside of the virus capsid. A major problem with such an approach is that the genes coding for these proteins have a very rapid mutation rate, forcing commercial producers to wait for mutations to occur before developing effective new versions of standard vaccines. However, a recent study has revealed that the 1918 flu virus, like the H5N1 avian flu virus, has an E627K mutation in its polymerase B2 component, which is located inside the virus capsid. Other research has indicated that this mutation strongly influences the virulence of H5N1. It seems reasonable to believe that the constancy, over more than 80 years, of the E627K mutation could be exploited to begin developing a vaccine now, rather than waiting for new mutations. Consequently, a publicly available database at the National Center for Biotechnology Information (NCBI) website, and the SYFPEITHI online computer algorithm, were used to generate a hypothesis about a peptide-based vaccine targeted at the E627K mutation in PB2 of the avian influenza virus. It was found that the peptide sequence, DTVQIIKLL, present in the PB2 protein of the H5N1 virus, would be expected to bind to HLA-A26 restricted immune system cell surface receptors. Hence, the bound peptide might be capable of stimulating protection from cytotoxic T lymphocytes. Should the present hypothesis be confirmed in laboratory studies, and an effective vaccine developed for individuals expressing the HLA-A26 receptor; further research would be indicated. This research would be aimed at determining whether molecular modifications to the DTVQIIKLL peptide could make it effective with other members of the HLA-A1 supertype to which HLA-A26 belongs. In addition to allowing vaccine development to begin now, this peptide-based approach would have the advantage of avoiding the use of dangerous, live, avian influenza virus during mass production.
authors.affiliation: Science and Technology Studies, St. Thomas University, Fredericton, NB, Canada. jgillis@stu.ca
authors.forename: John Stuart
authors.initials: JS
authors.lastname: Gillis
mesh_terms: D036022:Capsid Proteins / Q000276:immunology*; D022081:Cell Surface Extensions / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006388:Hemagglutinins / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology*; D009439:Neuraminidase / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D036022:Capsid Proteins; D006388:Hemagglutinins; D014765:Viral Vaccines; D009439:Neuraminidase