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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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Towards the knowledge-based design of universal influenza epitope ensemble vaccines
AU - Sheikh, Qamar M.
AU - Gatherer, Derek
AU - Reche, Pedro A.
AU - Flower, Darren R.
N1 - © The Author(s) 2016. Published by Oxford University Press.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
U2 - 10.1093/bioinformatics/btw399
DO - 10.1093/bioinformatics/btw399
M3 - Journal article
C2 - 27402904
VL - 32
SP - 3233
EP - 3239
JO - Bioinformatics
JF - Bioinformatics
SN - 1367-4803
IS - 21
ER -