title: Towards the knowledge-based design of universal influenza epitope ensemble vaccines.
abstract: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes.
  
  
  
  To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes.
  
  
  
  http://imed.med.ucm.es/Tools/episopt.html CONTACT: d.r.flower@aston.ac.uk.
authors.affiliation: School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Qamar M
authors.initials: QM
authors.lastname: Sheikh
authors.affiliation: Division of Biomedical & Life Sciences, Faculty of Health & Medicine, Lancaster University, Lancaster LA1 4YW, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Gatherer
authors.affiliation: Facultad de Medicina, Departamento de Microbiologia I, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Reche
authors.affiliation: School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
mesh_terms: D015496:CD4-Positive T-Lymphocytes; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007125:Immunogenetics; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*
chemical_list: D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines