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Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation

BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co‐circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study, we aimed to predict and map the diversity of CD8+ T‐cell epito...

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Autores principales: Qiu, Xueting, Duvvuri, Venkata R., Gubbay, Jonathan B., Webby, Richard J., Kayali, Ghazi, Bahl, Justin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963872/
https://www.ncbi.nlm.nih.gov/pubmed/28715148
http://dx.doi.org/10.1111/irv.12466
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author Qiu, Xueting
Duvvuri, Venkata R.
Gubbay, Jonathan B.
Webby, Richard J.
Kayali, Ghazi
Bahl, Justin
author_facet Qiu, Xueting
Duvvuri, Venkata R.
Gubbay, Jonathan B.
Webby, Richard J.
Kayali, Ghazi
Bahl, Justin
author_sort Qiu, Xueting
collection PubMed
description BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co‐circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study, we aimed to predict and map the diversity of CD8+ T‐cell epitopes among H5 hemagglutinin (HA) gene lineages to estimate CD8+ T‐cell immunity in humans induced by vaccine candidates. METHODS: A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage‐specific epitope analyses. Conserved epitopes were predicted from WHO‐endorsed vaccine candidates and representative clade‐defining strains by pairwise comparison with Immune Epitope Database (IEDB). The distribution of predicted epitopes was mapped to each HPAI H5 lineage. We assume that high similarity and conservancy of predicted epitopes from vaccine candidates among all circulating HPAI H5 lineages is correlated with high immunity. RESULTS: A total of 49 conserved CD8+ T‐cell epitopes were predicted at 28 different amino acid positions of the HA protein. Mapping these epitopes to the phylogenetic tree allowed us to develop epitope profiles, or “fingerprints,” for each HPAI H5 lineage. Vaccine epitope percentage analyses showed some epitope profiles were highly conserved for all H5 isolates and may be valuable for universal vaccine design. However, the positions with low coverage may explain why the vaccine candidates do not always function well. CONCLUSIONS: These findings demonstrate that our analytical approach to evaluate conserved CD8+ T‐cell epitope prediction in a phylogenetic framework may provide important insights for computational design of vaccine selection and future epitope‐based design.
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spelling pubmed-59638722018-05-30 Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation Qiu, Xueting Duvvuri, Venkata R. Gubbay, Jonathan B. Webby, Richard J. Kayali, Ghazi Bahl, Justin Influenza Other Respir Viruses Original Articles BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co‐circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study, we aimed to predict and map the diversity of CD8+ T‐cell epitopes among H5 hemagglutinin (HA) gene lineages to estimate CD8+ T‐cell immunity in humans induced by vaccine candidates. METHODS: A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage‐specific epitope analyses. Conserved epitopes were predicted from WHO‐endorsed vaccine candidates and representative clade‐defining strains by pairwise comparison with Immune Epitope Database (IEDB). The distribution of predicted epitopes was mapped to each HPAI H5 lineage. We assume that high similarity and conservancy of predicted epitopes from vaccine candidates among all circulating HPAI H5 lineages is correlated with high immunity. RESULTS: A total of 49 conserved CD8+ T‐cell epitopes were predicted at 28 different amino acid positions of the HA protein. Mapping these epitopes to the phylogenetic tree allowed us to develop epitope profiles, or “fingerprints,” for each HPAI H5 lineage. Vaccine epitope percentage analyses showed some epitope profiles were highly conserved for all H5 isolates and may be valuable for universal vaccine design. However, the positions with low coverage may explain why the vaccine candidates do not always function well. CONCLUSIONS: These findings demonstrate that our analytical approach to evaluate conserved CD8+ T‐cell epitope prediction in a phylogenetic framework may provide important insights for computational design of vaccine selection and future epitope‐based design. John Wiley and Sons Inc. 2017-08-12 2017-09 /pmc/articles/PMC5963872/ /pubmed/28715148 http://dx.doi.org/10.1111/irv.12466 Text en © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Qiu, Xueting
Duvvuri, Venkata R.
Gubbay, Jonathan B.
Webby, Richard J.
Kayali, Ghazi
Bahl, Justin
Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation
title Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation
title_full Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation
title_fullStr Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation
title_full_unstemmed Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation
title_short Lineage‐specific epitope profiles for HPAI H5 pre‐pandemic vaccine selection and evaluation
title_sort lineage‐specific epitope profiles for hpai h5 pre‐pandemic vaccine selection and evaluation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963872/
https://www.ncbi.nlm.nih.gov/pubmed/28715148
http://dx.doi.org/10.1111/irv.12466
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