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An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge

The parasite Theileria parva is the causative agent of East Coast fever (ECF), one of the most serious cattle diseases in sub-Saharan Africa, and directly impacts smallholder farmers’ livelihoods. There is an efficient live-parasite vaccine, but issues with transmission of vaccine strains, need of a...

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Autores principales: Svitek, Nicholas, Saya, Rosemary, Awino, Elias, Munyao, Stephen, Muriuki, Robert, Njoroge, Thomas, Pellé, Roger, Ndiwa, Nicholas, Poole, Jane, Gilbert, Sarah, Nene, Vishvanath, Steinaa, Lucilla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134044/
https://www.ncbi.nlm.nih.gov/pubmed/30245859
http://dx.doi.org/10.1038/s41541-018-0073-5
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author Svitek, Nicholas
Saya, Rosemary
Awino, Elias
Munyao, Stephen
Muriuki, Robert
Njoroge, Thomas
Pellé, Roger
Ndiwa, Nicholas
Poole, Jane
Gilbert, Sarah
Nene, Vishvanath
Steinaa, Lucilla
author_facet Svitek, Nicholas
Saya, Rosemary
Awino, Elias
Munyao, Stephen
Muriuki, Robert
Njoroge, Thomas
Pellé, Roger
Ndiwa, Nicholas
Poole, Jane
Gilbert, Sarah
Nene, Vishvanath
Steinaa, Lucilla
author_sort Svitek, Nicholas
collection PubMed
description The parasite Theileria parva is the causative agent of East Coast fever (ECF), one of the most serious cattle diseases in sub-Saharan Africa, and directly impacts smallholder farmers’ livelihoods. There is an efficient live-parasite vaccine, but issues with transmission of vaccine strains, need of a cold chain, and antibiotics limit its utilization. This has fostered research towards subunit vaccination. Cytotoxic T lymphocytes (CTL) are crucial in combating the infection by lysing T. parva-infected cells. Tp1 is an immunodominant CTL antigen, which induces Tp1-specific responses in 70–80% of cattle of the A18 or A18v haplotype during vaccination with the live vaccine. In this study, human adenovirus serotype 5 (HAd5) and modified vaccinia Ankara (MVA) were assessed for their ability to induce Tp1-specific immunity. Both viral vectors expressing the Tp1 antigen were inoculated in cattle by a heterologous prime-boost vaccination regimen. All 15 animals responded to Tp1 as determined by ELISpot. Of these, 14 reacted to the known Tp1 epitope, assayed by ELISpot and tetramer analyses, with CTL peaking 1-week post-MVA boost. Eleven animals developed CTL with specific cytotoxic activity towards peripheral blood mononuclear cells (PBMC) pulsed with the Tp1 epitope. Moreover, 36% of the animals with a Tp1 epitope-specific response survived a lethal challenge with T. parva 5 weeks post-MVA boost. Reduction of the parasitemia correlated with increased percentages of central memory lymphocytes in the Tp1 epitope-specific CD8(+) populations. These results indicate that Tp1 is a promising antigen to include in a subunit vaccine and central memory cells are crucial for clearing the parasite.
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spelling pubmed-61340442018-09-21 An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge Svitek, Nicholas Saya, Rosemary Awino, Elias Munyao, Stephen Muriuki, Robert Njoroge, Thomas Pellé, Roger Ndiwa, Nicholas Poole, Jane Gilbert, Sarah Nene, Vishvanath Steinaa, Lucilla NPJ Vaccines Article The parasite Theileria parva is the causative agent of East Coast fever (ECF), one of the most serious cattle diseases in sub-Saharan Africa, and directly impacts smallholder farmers’ livelihoods. There is an efficient live-parasite vaccine, but issues with transmission of vaccine strains, need of a cold chain, and antibiotics limit its utilization. This has fostered research towards subunit vaccination. Cytotoxic T lymphocytes (CTL) are crucial in combating the infection by lysing T. parva-infected cells. Tp1 is an immunodominant CTL antigen, which induces Tp1-specific responses in 70–80% of cattle of the A18 or A18v haplotype during vaccination with the live vaccine. In this study, human adenovirus serotype 5 (HAd5) and modified vaccinia Ankara (MVA) were assessed for their ability to induce Tp1-specific immunity. Both viral vectors expressing the Tp1 antigen were inoculated in cattle by a heterologous prime-boost vaccination regimen. All 15 animals responded to Tp1 as determined by ELISpot. Of these, 14 reacted to the known Tp1 epitope, assayed by ELISpot and tetramer analyses, with CTL peaking 1-week post-MVA boost. Eleven animals developed CTL with specific cytotoxic activity towards peripheral blood mononuclear cells (PBMC) pulsed with the Tp1 epitope. Moreover, 36% of the animals with a Tp1 epitope-specific response survived a lethal challenge with T. parva 5 weeks post-MVA boost. Reduction of the parasitemia correlated with increased percentages of central memory lymphocytes in the Tp1 epitope-specific CD8(+) populations. These results indicate that Tp1 is a promising antigen to include in a subunit vaccine and central memory cells are crucial for clearing the parasite. Nature Publishing Group UK 2018-09-11 /pmc/articles/PMC6134044/ /pubmed/30245859 http://dx.doi.org/10.1038/s41541-018-0073-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Svitek, Nicholas
Saya, Rosemary
Awino, Elias
Munyao, Stephen
Muriuki, Robert
Njoroge, Thomas
Pellé, Roger
Ndiwa, Nicholas
Poole, Jane
Gilbert, Sarah
Nene, Vishvanath
Steinaa, Lucilla
An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge
title An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge
title_full An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge
title_fullStr An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge
title_full_unstemmed An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge
title_short An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8(+) central memory T cells and confers partial protection against a lethal challenge
title_sort ad/mva vectored theileria parva antigen induces schizont-specific cd8(+) central memory t cells and confers partial protection against a lethal challenge
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134044/
https://www.ncbi.nlm.nih.gov/pubmed/30245859
http://dx.doi.org/10.1038/s41541-018-0073-5
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