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    Rights statement: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Bioinformatics following peer review. The definitive publisher-authenticated version Qamar M Sheikh, Derek Gatherer, Pedro A Reche, and Darren R Flower Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines Bioinformatics first published online July 10, 2016 doi:10.1093/bioinformatics/btw399 is available online at:

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    Available under license: CC BY-NC: Creative Commons Attribution-NonCommercial 4.0 International License

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Towards the knowledge-based design of universal influenza epitope ensemble vaccines

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<mark>Journal publication date</mark>1/11/2016
<mark>Journal</mark>Bioinformatics
Issue number21
Volume32
Number of pages7
Pages (from-to)3233-3239
Publication StatusPublished
Early online date10/07/16
<mark>Original language</mark>English

Abstract

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 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.

AVAILABILITY: http://imed.med.ucm.es/EPISOPT.html CONTACT: d.r.flower@aston.ac.uk SUPPLEMENTARY INFORMATION: none.