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Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control

BACKGROUND: Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based del...

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Autores principales: Brewer, Kimberly D., Weir, Genevieve M., Dude, Iulia, Davis, Christa, Parsons, Cathryn, Penwell, Andrea, Rajagopalan, Rajkannan, Sammatur, Leeladhar, Bowen, Chris V., Stanford, Marianne M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787234/
https://www.ncbi.nlm.nih.gov/pubmed/29374458
http://dx.doi.org/10.1186/s12929-018-0413-9
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author Brewer, Kimberly D.
Weir, Genevieve M.
Dude, Iulia
Davis, Christa
Parsons, Cathryn
Penwell, Andrea
Rajagopalan, Rajkannan
Sammatur, Leeladhar
Bowen, Chris V.
Stanford, Marianne M.
author_facet Brewer, Kimberly D.
Weir, Genevieve M.
Dude, Iulia
Davis, Christa
Parsons, Cathryn
Penwell, Andrea
Rajagopalan, Rajkannan
Sammatur, Leeladhar
Bowen, Chris V.
Stanford, Marianne M.
author_sort Brewer, Kimberly D.
collection PubMed
description BACKGROUND: Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based delivery system that directly suspends the vaccine components in the oil diluent that forces immune cells to actively take up components from the formulation in the absence of passive release. The aim of this study was to use magnetic resonance imaging (MRI) with additional biological markers to evaluate and understand differences in clearance between several different delivery systems used in peptide-based cancer vaccines. METHODS: C57BL/6 mice were implanted with a cervical cancer model and vaccinated 5 days post-implant with either DepoVax (DPX), a water-in-oil emulsion (w/o), a squalene oil-in-water emulsion (squal o/w) or a saponin/liposome emulsion (sap/lip) containing iron oxide-labeled targeted antigen. MRI was then used to monitor antigen clearance, the site of injection, tumour and inguinal lymph node volumes and other gross anatomical changes. HLA-A2 transgenic mice were also vaccinated to evaluate immune responses of human directed peptides. RESULTS: We demonstrated differences in antigen clearance between DPX and w/o both in regard to how quickly the antigen was cleared and the pattern in which it was cleared. We also found differences in lymph node responses between DPX and both squal o/w and sap/lip. CONCLUSIONS: These studies underline the unique mechanism of action of this clinical stage vaccine delivery system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-018-0413-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-57872342018-02-08 Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control Brewer, Kimberly D. Weir, Genevieve M. Dude, Iulia Davis, Christa Parsons, Cathryn Penwell, Andrea Rajagopalan, Rajkannan Sammatur, Leeladhar Bowen, Chris V. Stanford, Marianne M. J Biomed Sci Research BACKGROUND: Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based delivery system that directly suspends the vaccine components in the oil diluent that forces immune cells to actively take up components from the formulation in the absence of passive release. The aim of this study was to use magnetic resonance imaging (MRI) with additional biological markers to evaluate and understand differences in clearance between several different delivery systems used in peptide-based cancer vaccines. METHODS: C57BL/6 mice were implanted with a cervical cancer model and vaccinated 5 days post-implant with either DepoVax (DPX), a water-in-oil emulsion (w/o), a squalene oil-in-water emulsion (squal o/w) or a saponin/liposome emulsion (sap/lip) containing iron oxide-labeled targeted antigen. MRI was then used to monitor antigen clearance, the site of injection, tumour and inguinal lymph node volumes and other gross anatomical changes. HLA-A2 transgenic mice were also vaccinated to evaluate immune responses of human directed peptides. RESULTS: We demonstrated differences in antigen clearance between DPX and w/o both in regard to how quickly the antigen was cleared and the pattern in which it was cleared. We also found differences in lymph node responses between DPX and both squal o/w and sap/lip. CONCLUSIONS: These studies underline the unique mechanism of action of this clinical stage vaccine delivery system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-018-0413-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-27 /pmc/articles/PMC5787234/ /pubmed/29374458 http://dx.doi.org/10.1186/s12929-018-0413-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Brewer, Kimberly D.
Weir, Genevieve M.
Dude, Iulia
Davis, Christa
Parsons, Cathryn
Penwell, Andrea
Rajagopalan, Rajkannan
Sammatur, Leeladhar
Bowen, Chris V.
Stanford, Marianne M.
Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
title Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
title_full Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
title_fullStr Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
title_full_unstemmed Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
title_short Unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
title_sort unique depot formed by an oil based vaccine facilitates active antigen uptake and provides effective tumour control
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787234/
https://www.ncbi.nlm.nih.gov/pubmed/29374458
http://dx.doi.org/10.1186/s12929-018-0413-9
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