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Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza

Background  The best form of protection against influenza is high‐titred virus‐neutralizing antibody specific for the challenge strain. However, this is not always possible to achieve by vaccination due to the need for predicting the emerging virus, whether it be a drift variant of existing human en...

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Autores principales: Ng, Wy Ching, Gilbertson, Brad, Lim, Bock, Zeng, Weiguang, Jackson, David C., Brown, Lorena E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634688/
https://www.ncbi.nlm.nih.gov/pubmed/19627375
http://dx.doi.org/10.1111/j.1750-2659.2009.00087.x
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author Ng, Wy Ching
Gilbertson, Brad
Lim, Bock
Zeng, Weiguang
Jackson, David C.
Brown, Lorena E.
author_facet Ng, Wy Ching
Gilbertson, Brad
Lim, Bock
Zeng, Weiguang
Jackson, David C.
Brown, Lorena E.
author_sort Ng, Wy Ching
collection PubMed
description Background  The best form of protection against influenza is high‐titred virus‐neutralizing antibody specific for the challenge strain. However, this is not always possible to achieve by vaccination due to the need for predicting the emerging virus, whether it be a drift variant of existing human endemic influenza type A subtypes or the next pandemic virus, for incorporation into the vaccine. By activating additional arms of the immune system to provide heterosubtypic immunity, that is immunity active against all viruses of type A influenza regardless of subtype or strain, it should be possible to provide significant benefit in situations where appropriate antibody responses are not achieved. Although current inactivated vaccines are unable to induce heterosubtypic CD8(+) T cell immunity, we have shown that lipopeptides are particularly efficient in this regard. Objectives  To examine the role of vaccine‐induced CD8(+) T cells in altering the course of disease due to highly virulent H1N1 influenza virus in the mouse model. Methods  The induction of influenza‐specific CD8(+) T cells following intranasal inoculation with lipopeptide vaccine was assessed by intracellular cytokine staining (ICS) and the capacity of these cells to reduce viral loads in the lungs and to protect against death after viral challenge was determined. Results and conclusions  We show that CD8(+) T cells are induced by a single intranasal vaccination with lipopeptide, they remain at substantial levels in the lungs and are efficiently boosted upon challenge with virulent virus to provide late control of pulmonary viral loads. Vaccinated mice are not only protected from death but remain active, indicative of less severe disease despite significant weight loss.
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spelling pubmed-46346882015-11-27 Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza Ng, Wy Ching Gilbertson, Brad Lim, Bock Zeng, Weiguang Jackson, David C. Brown, Lorena E. Influenza Other Respir Viruses Original Articles Background  The best form of protection against influenza is high‐titred virus‐neutralizing antibody specific for the challenge strain. However, this is not always possible to achieve by vaccination due to the need for predicting the emerging virus, whether it be a drift variant of existing human endemic influenza type A subtypes or the next pandemic virus, for incorporation into the vaccine. By activating additional arms of the immune system to provide heterosubtypic immunity, that is immunity active against all viruses of type A influenza regardless of subtype or strain, it should be possible to provide significant benefit in situations where appropriate antibody responses are not achieved. Although current inactivated vaccines are unable to induce heterosubtypic CD8(+) T cell immunity, we have shown that lipopeptides are particularly efficient in this regard. Objectives  To examine the role of vaccine‐induced CD8(+) T cells in altering the course of disease due to highly virulent H1N1 influenza virus in the mouse model. Methods  The induction of influenza‐specific CD8(+) T cells following intranasal inoculation with lipopeptide vaccine was assessed by intracellular cytokine staining (ICS) and the capacity of these cells to reduce viral loads in the lungs and to protect against death after viral challenge was determined. Results and conclusions  We show that CD8(+) T cells are induced by a single intranasal vaccination with lipopeptide, they remain at substantial levels in the lungs and are efficiently boosted upon challenge with virulent virus to provide late control of pulmonary viral loads. Vaccinated mice are not only protected from death but remain active, indicative of less severe disease despite significant weight loss. Blackwell Publishing Ltd 2009-06-15 2009-07 /pmc/articles/PMC4634688/ /pubmed/19627375 http://dx.doi.org/10.1111/j.1750-2659.2009.00087.x Text en © 2009 Blackwell Publishing Ltd
spellingShingle Original Articles
Ng, Wy Ching
Gilbertson, Brad
Lim, Bock
Zeng, Weiguang
Jackson, David C.
Brown, Lorena E.
Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza
title Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza
title_full Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza
title_fullStr Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza
title_full_unstemmed Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza
title_short Lipopeptide vaccines illustrate the potential role of subtype‐crossreactive T cells in the control of highly virulent influenza
title_sort lipopeptide vaccines illustrate the potential role of subtype‐crossreactive t cells in the control of highly virulent influenza
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634688/
https://www.ncbi.nlm.nih.gov/pubmed/19627375
http://dx.doi.org/10.1111/j.1750-2659.2009.00087.x
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