Título: | Towards the Knowledge-based Design of UniversalInfluenza Epitope Ensemble Vaccines |
Autores: | Sheikh, Qamar M ; Gatherer, Derek ; Reche, Pedro A ; Flower, Darren R |
Tipo de documento: | texto impreso |
Editorial: | Oxford University Pres, 2016-07 |
Dimensiones: | application/pdf |
Nota general: |
cc_by info:eu-repo/semantics/openAccess |
Idiomas: | |
Palabras clave: | Estado = Publicado , Materia = Ciencias: Informática: Bioinformática , Materia = Ciencias Biomédicas: Medicina: Microbiología médica , Tipo = Artículo |
Resumen: |
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. |
En línea: | https://eprints.ucm.es/39499/1/Bioinformatics-2016-Sheikh-bioinformatics-btw399.pdf |
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