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Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines

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Sheikh, Qamar M and Gatherer, Derek and Reche, Pedro A and Flower, Darren R (2016) Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines. Bioinformatics Advance . pp. 1-7. ISSN 1460-2059

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Official URL: http://bioinformatics.oxfordjournals.org/content/early/2016/08/16/bioinformatics.btw399.full.pdf+html?sid=2457af8d-582c-48f2-94ff-b71209acab0f



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 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.


Item Type:Article
Uncontrolled Keywords:Vaccines
Subjects:Sciences > Computer science > Bioinformatics
Medical sciences > Medicine > Medical microbiology
ID Code:39499
Deposited On:18 Oct 2016 12:25
Last Modified:13 Dec 2018 12:48

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