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The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV

Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy; novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major...

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Autores principales: Chinnakannan, Senthil K., Cargill, Tamsin N., Donnison, Timothy A., Ansari, M. Azim, Sebastian, Sarah, Lee, Lian Ni, Hutchings, Claire, Klenerman, Paul, Maini, Mala K., Evans, Tom, Barnes, Eleanor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348829/
https://www.ncbi.nlm.nih.gov/pubmed/32295168
http://dx.doi.org/10.3390/vaccines8020184
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author Chinnakannan, Senthil K.
Cargill, Tamsin N.
Donnison, Timothy A.
Ansari, M. Azim
Sebastian, Sarah
Lee, Lian Ni
Hutchings, Claire
Klenerman, Paul
Maini, Mala K.
Evans, Tom
Barnes, Eleanor
author_facet Chinnakannan, Senthil K.
Cargill, Tamsin N.
Donnison, Timothy A.
Ansari, M. Azim
Sebastian, Sarah
Lee, Lian Ni
Hutchings, Claire
Klenerman, Paul
Maini, Mala K.
Evans, Tom
Barnes, Eleanor
author_sort Chinnakannan, Senthil K.
collection PubMed
description Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy; novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFNγ, TNF-α, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection.
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spelling pubmed-73488292020-07-22 The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV Chinnakannan, Senthil K. Cargill, Tamsin N. Donnison, Timothy A. Ansari, M. Azim Sebastian, Sarah Lee, Lian Ni Hutchings, Claire Klenerman, Paul Maini, Mala K. Evans, Tom Barnes, Eleanor Vaccines (Basel) Article Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy; novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFNγ, TNF-α, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection. MDPI 2020-04-14 /pmc/articles/PMC7348829/ /pubmed/32295168 http://dx.doi.org/10.3390/vaccines8020184 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chinnakannan, Senthil K.
Cargill, Tamsin N.
Donnison, Timothy A.
Ansari, M. Azim
Sebastian, Sarah
Lee, Lian Ni
Hutchings, Claire
Klenerman, Paul
Maini, Mala K.
Evans, Tom
Barnes, Eleanor
The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
title The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
title_full The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
title_fullStr The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
title_full_unstemmed The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
title_short The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV
title_sort design and development of a multi-hbv antigen encoded in chimpanzee adenoviral and modified vaccinia ankara viral vectors; a novel therapeutic vaccine strategy against hbv
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348829/
https://www.ncbi.nlm.nih.gov/pubmed/32295168
http://dx.doi.org/10.3390/vaccines8020184
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