Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation

Induction of antigen-specific CD8+ T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8+ T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modifie...

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Main Authors:	Ewer, Katie J., O’Hara, Geraldine A., Duncan, Christopher J. A., Collins, Katharine A., Sheehy, Susanne H., Reyes-Sandoval, Arturo, Goodman, Anna L., Edwards, Nick J., Elias, Sean C., Halstead, Fenella D., Longley, Rhea J., Rowland, Rosalind, Poulton, Ian D., Draper, Simon J., Blagborough, Andrew M., Berrie, Eleanor, Moyle, Sarah, Williams, Nicola, Siani, Loredana, Folgori, Antonella, Colloca, Stefano, Sinden, Robert E., Lawrie, Alison M., Cortese, Riccardo, Gilbert, Sarah C., Nicosia, Alfredo, Hill, Adrian V. S.
Format:	Online
Language:	English
Published:	Nature Pub. Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868203/

id	pubmed-3868203
recordtype	oai_dc
spelling	pubmed-38682032013-12-20 Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation Ewer, Katie J. O’Hara, Geraldine A. Duncan, Christopher J. A. Collins, Katharine A. Sheehy, Susanne H. Reyes-Sandoval, Arturo Goodman, Anna L. Edwards, Nick J. Elias, Sean C. Halstead, Fenella D. Longley, Rhea J. Rowland, Rosalind Poulton, Ian D. Draper, Simon J. Blagborough, Andrew M. Berrie, Eleanor Moyle, Sarah Williams, Nicola Siani, Loredana Folgori, Antonella Colloca, Stefano Sinden, Robert E. Lawrie, Alison M. Cortese, Riccardo Gilbert, Sarah C. Nicosia, Alfredo Hill, Adrian V. S. Article Induction of antigen-specific CD8+ T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8+ T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/106 peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8+ T cells, but not antibodies, correlates with sterile protection and delay in time to patency (Pcorrected=0.005). Vaccine-induced CD8+ T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells. Nature Pub. Group 2013-11-28 /pmc/articles/PMC3868203/ /pubmed/24284865 http://dx.doi.org/10.1038/ncomms3836 Text en Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-by/3.0/ This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ewer, Katie J. O’Hara, Geraldine A. Duncan, Christopher J. A. Collins, Katharine A. Sheehy, Susanne H. Reyes-Sandoval, Arturo Goodman, Anna L. Edwards, Nick J. Elias, Sean C. Halstead, Fenella D. Longley, Rhea J. Rowland, Rosalind Poulton, Ian D. Draper, Simon J. Blagborough, Andrew M. Berrie, Eleanor Moyle, Sarah Williams, Nicola Siani, Loredana Folgori, Antonella Colloca, Stefano Sinden, Robert E. Lawrie, Alison M. Cortese, Riccardo Gilbert, Sarah C. Nicosia, Alfredo Hill, Adrian V. S.
spellingShingle	Ewer, Katie J. O’Hara, Geraldine A. Duncan, Christopher J. A. Collins, Katharine A. Sheehy, Susanne H. Reyes-Sandoval, Arturo Goodman, Anna L. Edwards, Nick J. Elias, Sean C. Halstead, Fenella D. Longley, Rhea J. Rowland, Rosalind Poulton, Ian D. Draper, Simon J. Blagborough, Andrew M. Berrie, Eleanor Moyle, Sarah Williams, Nicola Siani, Loredana Folgori, Antonella Colloca, Stefano Sinden, Robert E. Lawrie, Alison M. Cortese, Riccardo Gilbert, Sarah C. Nicosia, Alfredo Hill, Adrian V. S. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
author_facet	Ewer, Katie J. O’Hara, Geraldine A. Duncan, Christopher J. A. Collins, Katharine A. Sheehy, Susanne H. Reyes-Sandoval, Arturo Goodman, Anna L. Edwards, Nick J. Elias, Sean C. Halstead, Fenella D. Longley, Rhea J. Rowland, Rosalind Poulton, Ian D. Draper, Simon J. Blagborough, Andrew M. Berrie, Eleanor Moyle, Sarah Williams, Nicola Siani, Loredana Folgori, Antonella Colloca, Stefano Sinden, Robert E. Lawrie, Alison M. Cortese, Riccardo Gilbert, Sarah C. Nicosia, Alfredo Hill, Adrian V. S.
author_sort	Ewer, Katie J.
title	Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
title_short	Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
title_full	Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
title_fullStr	Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
title_full_unstemmed	Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
title_sort	protective cd8+ t-cell immunity to human malaria induced by chimpanzee adenovirus-mva immunisation
description	Induction of antigen-specific CD8+ T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8+ T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/106 peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8+ T cells, but not antibodies, correlates with sterile protection and delay in time to patency (Pcorrected=0.005). Vaccine-induced CD8+ T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.
publisher	Nature Pub. Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868203/
_version_	1612039989321793536

Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation

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