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Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype
Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481277/ https://www.ncbi.nlm.nih.gov/pubmed/26167164 http://dx.doi.org/10.3389/fimmu.2015.00329 |
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author | Mallajosyula, V. Vamsee Aditya Citron, Michael Ferrara, Francesca Temperton, Nigel J. Liang, Xiaoping Flynn, Jessica A. Varadarajan, Raghavan |
author_facet | Mallajosyula, V. Vamsee Aditya Citron, Michael Ferrara, Francesca Temperton, Nigel J. Liang, Xiaoping Flynn, Jessica A. Varadarajan, Raghavan |
author_sort | Mallajosyula, V. Vamsee Aditya |
collection | PubMed |
description | Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. Influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (HA). However, the predominant humoral response is against the hypervariable head domain of HA, thereby restricting the breadth of protection. In contrast, the conserved, subdominant stem domain of HA is a potential “universal” vaccine candidate. We designed an HA stem-fragment immunogen from the 1968 pandemic H3N2 strain (A/Hong Kong/1/68) guided by a comprehensive H3 HA sequence conservation analysis. The biophysical properties of the designed immunogen were further improved by C-terminal fusion of a trimerization motif, “isoleucine-zipper”, or “foldon”. These immunogens elicited cross-reactive, antiviral antibodies and conferred partial protection against a lethal, homologous HK68 virus challenge in vivo. Furthermore, bacterial expression of these immunogens is economical and facilitates rapid scale-up. |
format | Online Article Text |
id | pubmed-4481277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44812772015-07-10 Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype Mallajosyula, V. Vamsee Aditya Citron, Michael Ferrara, Francesca Temperton, Nigel J. Liang, Xiaoping Flynn, Jessica A. Varadarajan, Raghavan Front Immunol Immunology Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. Influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (HA). However, the predominant humoral response is against the hypervariable head domain of HA, thereby restricting the breadth of protection. In contrast, the conserved, subdominant stem domain of HA is a potential “universal” vaccine candidate. We designed an HA stem-fragment immunogen from the 1968 pandemic H3N2 strain (A/Hong Kong/1/68) guided by a comprehensive H3 HA sequence conservation analysis. The biophysical properties of the designed immunogen were further improved by C-terminal fusion of a trimerization motif, “isoleucine-zipper”, or “foldon”. These immunogens elicited cross-reactive, antiviral antibodies and conferred partial protection against a lethal, homologous HK68 virus challenge in vivo. Furthermore, bacterial expression of these immunogens is economical and facilitates rapid scale-up. Frontiers Media S.A. 2015-06-26 /pmc/articles/PMC4481277/ /pubmed/26167164 http://dx.doi.org/10.3389/fimmu.2015.00329 Text en Copyright © 2015 Mallajosyula, Citron, Ferrara, Temperton, Liang, Flynn and Varadarajan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Mallajosyula, V. Vamsee Aditya Citron, Michael Ferrara, Francesca Temperton, Nigel J. Liang, Xiaoping Flynn, Jessica A. Varadarajan, Raghavan Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype |
title | Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype |
title_full | Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype |
title_fullStr | Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype |
title_full_unstemmed | Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype |
title_short | Hemagglutinin Sequence Conservation Guided Stem Immunogen Design from Influenza A H3 Subtype |
title_sort | hemagglutinin sequence conservation guided stem immunogen design from influenza a h3 subtype |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481277/ https://www.ncbi.nlm.nih.gov/pubmed/26167164 http://dx.doi.org/10.3389/fimmu.2015.00329 |
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