Synthetic multi-epitope peptides identified in silico induce protective immunity against multiple influenza serotypes.
Influenza causes yearly epidemics of mild disease and, occasionally, pandemics with millions of fatalities. Currently, no vaccine is effective against all influenza strains. Analysis of influenza sequences from animal and human isolates using CLUSTALW and a novel proprietary epitope prediction algorithm identified six conserved T cell-reactive regions in several proteins. Immunisation of transgenic mice with a preparation of these six regions as chemically synthesised peptides (FLU-v) induced a specific HLA-A*0201-mediated CD8(+) T cell response. This T cell population also reacted against human cells infected with three non-related influenza strains, confirming that the identified regions contain epitopes naturally presented by infected human cells and conserved amongst non-related viruses. Moreover, FLU-v immunisation significantly increased survival of transgenic mice against lethal challenge with influenza. Overall, FLU-v represents a promising influenza vaccine candidate, obviating the need for yearly vaccinations and allowing the stockpiling and initiation of a worldwide vaccination program in advance of a pandemic outbreak.
Stoloff
Gregory A
GA
PepTcell Limited, High Wycombe, UK.
Caparros-Wanderley
Wilson
W
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000276:immunology*; D009981:Influenza B virus / Q000145:classification / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D012703:Serotyping; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006649:Histocompatibility Antigens; D010446:Peptide Fragments; D014764:Viral Proteins; D007371:Interferon-gamma