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Reche Gallardo, Pedro Antonio Sheikh, Qamar M Gatherer, Derek Flower, Darren R 2023-06-18T06:57:02Z 2023-06-18T06:57:02Z 2016-07 1460-2059 10.1093/bioinformatics/btw399 https://hdl.handle.net/20.500.14352/24653 http://bioinformatics.oxfordjournals.org/content/early/2016/08/16/bioinformatics.btw399.full.pdf+html?sid=2457af8d-582c-48f2-94ff-b71209acab0f Motivation: 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. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highlyconserved 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. eng https://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines journal article