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Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy

Monoclonal antibodies are widely used to treat non-infectious conditions but are costly. Vaccines could offer a cost-effective alternative but have been limited by sub-optimal T-cell stimulation and/or weak vaccine responses in recipients, for example, in elderly patients. We have previously shown t...

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Autores principales: Zeltins, Andris, West, Jonathan, Zabel, Franziska, El Turabi, Aadil, Balke, Ina, Haas, Stefanie, Maudrich, Melanie, Storni, Federico, Engeroff, Paul, Jennings, Gary T., Kotecha, Abhay, Stuart, David I, Foerster, John, Bachmann, Martin F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653761/
https://www.ncbi.nlm.nih.gov/pubmed/29263885
http://dx.doi.org/10.1038/s41541-017-0030-8
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author Zeltins, Andris
West, Jonathan
Zabel, Franziska
El Turabi, Aadil
Balke, Ina
Haas, Stefanie
Maudrich, Melanie
Storni, Federico
Engeroff, Paul
Jennings, Gary T.
Kotecha, Abhay
Stuart, David I
Foerster, John
Bachmann, Martin F.
author_facet Zeltins, Andris
West, Jonathan
Zabel, Franziska
El Turabi, Aadil
Balke, Ina
Haas, Stefanie
Maudrich, Melanie
Storni, Federico
Engeroff, Paul
Jennings, Gary T.
Kotecha, Abhay
Stuart, David I
Foerster, John
Bachmann, Martin F.
author_sort Zeltins, Andris
collection PubMed
description Monoclonal antibodies are widely used to treat non-infectious conditions but are costly. Vaccines could offer a cost-effective alternative but have been limited by sub-optimal T-cell stimulation and/or weak vaccine responses in recipients, for example, in elderly patients. We have previously shown that the repetitive structure of virus-like-particles (VLPs) can effectively bypass self-tolerance in therapeutic vaccines. Their efficacy could be increased even further by the incorporation of an epitope stimulating T cell help. However, the self-assembly and stability of VLPs from envelope monomer proteins is sensitive to geometry, rendering the incorporation of foreign epitopes difficult. We here show that it is possible to engineer VLPs derived from a non human-pathogenic plant virus to incorporate a powerful T-cell-stimulatory epitope derived from Tetanus toxoid. These VLPs (termed CMV(TT)) retain self-assembly as well as long-term stability. Since Th cell memory to Tetanus is near universal in humans, CMV(TT)-based vaccines can deliver robust antibody-responses even under limiting conditions. By way of proof of concept, we tested a range of such vaccines against chronic inflammatory conditions (model: psoriasis, antigen: interleukin-17), neurodegenerative (Alzheimer’s, β-amyloid), and allergic disease (cat allergy, Fel-d1), respectively. Vaccine responses were uniformly strong, selective, efficient in vivo, observed even in old mice, and employing low vaccine doses. In addition, randomly ascertained human blood cells were reactive to CMV(TT)-VLPs, confirming recognition of the incorporated Tetanus epitope. The CMV(TT)-VLP platform is adaptable to almost any antigen and its features and performance are ideally suited for the design of vaccines delivering enhanced responsiveness in aging populations.
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spelling pubmed-56537612017-12-20 Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy Zeltins, Andris West, Jonathan Zabel, Franziska El Turabi, Aadil Balke, Ina Haas, Stefanie Maudrich, Melanie Storni, Federico Engeroff, Paul Jennings, Gary T. Kotecha, Abhay Stuart, David I Foerster, John Bachmann, Martin F. NPJ Vaccines Article Monoclonal antibodies are widely used to treat non-infectious conditions but are costly. Vaccines could offer a cost-effective alternative but have been limited by sub-optimal T-cell stimulation and/or weak vaccine responses in recipients, for example, in elderly patients. We have previously shown that the repetitive structure of virus-like-particles (VLPs) can effectively bypass self-tolerance in therapeutic vaccines. Their efficacy could be increased even further by the incorporation of an epitope stimulating T cell help. However, the self-assembly and stability of VLPs from envelope monomer proteins is sensitive to geometry, rendering the incorporation of foreign epitopes difficult. We here show that it is possible to engineer VLPs derived from a non human-pathogenic plant virus to incorporate a powerful T-cell-stimulatory epitope derived from Tetanus toxoid. These VLPs (termed CMV(TT)) retain self-assembly as well as long-term stability. Since Th cell memory to Tetanus is near universal in humans, CMV(TT)-based vaccines can deliver robust antibody-responses even under limiting conditions. By way of proof of concept, we tested a range of such vaccines against chronic inflammatory conditions (model: psoriasis, antigen: interleukin-17), neurodegenerative (Alzheimer’s, β-amyloid), and allergic disease (cat allergy, Fel-d1), respectively. Vaccine responses were uniformly strong, selective, efficient in vivo, observed even in old mice, and employing low vaccine doses. In addition, randomly ascertained human blood cells were reactive to CMV(TT)-VLPs, confirming recognition of the incorporated Tetanus epitope. The CMV(TT)-VLP platform is adaptable to almost any antigen and its features and performance are ideally suited for the design of vaccines delivering enhanced responsiveness in aging populations. Nature Publishing Group UK 2017-10-23 /pmc/articles/PMC5653761/ /pubmed/29263885 http://dx.doi.org/10.1038/s41541-017-0030-8 Text en © The Author(s) 2017 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
Zeltins, Andris
West, Jonathan
Zabel, Franziska
El Turabi, Aadil
Balke, Ina
Haas, Stefanie
Maudrich, Melanie
Storni, Federico
Engeroff, Paul
Jennings, Gary T.
Kotecha, Abhay
Stuart, David I
Foerster, John
Bachmann, Martin F.
Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
title Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
title_full Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
title_fullStr Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
title_full_unstemmed Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
title_short Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
title_sort incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, alzheimer’s and cat allergy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653761/
https://www.ncbi.nlm.nih.gov/pubmed/29263885
http://dx.doi.org/10.1038/s41541-017-0030-8
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