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Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice
Adenoviral (Ad) vectors represent promising vaccine platforms for infectious disease. To overcome pre-existing immunity to commonly used human adenovirus serotype 5 (Ad5), vectors based on rare species or non-human Ads are being developed. However, these vectors often exhibit reduced potency compare...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953706/ https://www.ncbi.nlm.nih.gov/pubmed/31934599 http://dx.doi.org/10.1016/j.omtm.2019.12.003 |
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author | Bliss, Carly M. Parsons, Andrea J. Nachbagauer, Raffael Hamilton, Jennifer R. Cappuccini, Federica Ulaszewska, Marta Webber, Jason P. Clayton, Aled Hill, Adrian V.S. Coughlan, Lynda |
author_facet | Bliss, Carly M. Parsons, Andrea J. Nachbagauer, Raffael Hamilton, Jennifer R. Cappuccini, Federica Ulaszewska, Marta Webber, Jason P. Clayton, Aled Hill, Adrian V.S. Coughlan, Lynda |
author_sort | Bliss, Carly M. |
collection | PubMed |
description | Adenoviral (Ad) vectors represent promising vaccine platforms for infectious disease. To overcome pre-existing immunity to commonly used human adenovirus serotype 5 (Ad5), vectors based on rare species or non-human Ads are being developed. However, these vectors often exhibit reduced potency compared with Ad5, necessitating the use of innovative approaches to augment the immunogenicity of the encoded antigen (Ag). To achieve this, we engineered model Ag, enhanced green fluorescent protein (EGFP), for targeting to the surface of host-derived extracellular vesicles (EVs), namely exosomes. Exosomes are nano-sized EVs that play important roles in cell-to-cell communication and in regulating immune responses. Directed targeting of Ag to the surface of EVs/exosomes is achieved by “exosome display,” through fusion of Ag to the C1C2 domain of lactadherin, a protein highly enriched in exosomes. Herein, we engineered chimpanzee adenovirus ChAdOx1 and Ad5-based vaccines encoding EGFP, or EGFP targeted to EVs (EGFP_C1C2), and compared vaccine immunogenicity in mice. We determined that exosome display substantially increases Ag-specific humoral immunity following intramuscular and intranasal vaccination, improving the immunological potency of both ChAdOx1 and Ad5. We propose that this Ag-engineering approach could increase the immunogenicity of diverse Ad vectors that exhibit desirable manufacturing characteristics, but currently lack the potency of Ad5. |
format | Online Article Text |
id | pubmed-6953706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-69537062020-01-13 Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice Bliss, Carly M. Parsons, Andrea J. Nachbagauer, Raffael Hamilton, Jennifer R. Cappuccini, Federica Ulaszewska, Marta Webber, Jason P. Clayton, Aled Hill, Adrian V.S. Coughlan, Lynda Mol Ther Methods Clin Dev Article Adenoviral (Ad) vectors represent promising vaccine platforms for infectious disease. To overcome pre-existing immunity to commonly used human adenovirus serotype 5 (Ad5), vectors based on rare species or non-human Ads are being developed. However, these vectors often exhibit reduced potency compared with Ad5, necessitating the use of innovative approaches to augment the immunogenicity of the encoded antigen (Ag). To achieve this, we engineered model Ag, enhanced green fluorescent protein (EGFP), for targeting to the surface of host-derived extracellular vesicles (EVs), namely exosomes. Exosomes are nano-sized EVs that play important roles in cell-to-cell communication and in regulating immune responses. Directed targeting of Ag to the surface of EVs/exosomes is achieved by “exosome display,” through fusion of Ag to the C1C2 domain of lactadherin, a protein highly enriched in exosomes. Herein, we engineered chimpanzee adenovirus ChAdOx1 and Ad5-based vaccines encoding EGFP, or EGFP targeted to EVs (EGFP_C1C2), and compared vaccine immunogenicity in mice. We determined that exosome display substantially increases Ag-specific humoral immunity following intramuscular and intranasal vaccination, improving the immunological potency of both ChAdOx1 and Ad5. We propose that this Ag-engineering approach could increase the immunogenicity of diverse Ad vectors that exhibit desirable manufacturing characteristics, but currently lack the potency of Ad5. American Society of Gene & Cell Therapy 2019-12-24 /pmc/articles/PMC6953706/ /pubmed/31934599 http://dx.doi.org/10.1016/j.omtm.2019.12.003 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Bliss, Carly M. Parsons, Andrea J. Nachbagauer, Raffael Hamilton, Jennifer R. Cappuccini, Federica Ulaszewska, Marta Webber, Jason P. Clayton, Aled Hill, Adrian V.S. Coughlan, Lynda Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice |
title | Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice |
title_full | Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice |
title_fullStr | Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice |
title_full_unstemmed | Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice |
title_short | Targeting Antigen to the Surface of EVs Improves the In Vivo Immunogenicity of Human and Non-human Adenoviral Vaccines in Mice |
title_sort | targeting antigen to the surface of evs improves the in vivo immunogenicity of human and non-human adenoviral vaccines in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953706/ https://www.ncbi.nlm.nih.gov/pubmed/31934599 http://dx.doi.org/10.1016/j.omtm.2019.12.003 |
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