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In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines

Intrinsic or added immune activating molecules are key for most vaccines to provide desired immunity profiles but may increase systemic reactogenicity. Regulatory agencies require rabbit pyrogen testing (RPT) for demonstration of vaccine reactogenicity. Recently, the monocyte activation test (MAT) g...

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Autores principales: Molenaar-de Backer, Marijke W. A., Doodeman, Paulien, Rezai, Fereshte, Verhagen, Lisa M., van der Ark, Arno, Plagmeijer, Els M., Metz, Bernard, van Vlies, Naomi, Ophorst, Olga, Raeven, René H. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403550/
https://www.ncbi.nlm.nih.gov/pubmed/37542099
http://dx.doi.org/10.1038/s41598-023-39908-7
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author Molenaar-de Backer, Marijke W. A.
Doodeman, Paulien
Rezai, Fereshte
Verhagen, Lisa M.
van der Ark, Arno
Plagmeijer, Els M.
Metz, Bernard
van Vlies, Naomi
Ophorst, Olga
Raeven, René H. M.
author_facet Molenaar-de Backer, Marijke W. A.
Doodeman, Paulien
Rezai, Fereshte
Verhagen, Lisa M.
van der Ark, Arno
Plagmeijer, Els M.
Metz, Bernard
van Vlies, Naomi
Ophorst, Olga
Raeven, René H. M.
author_sort Molenaar-de Backer, Marijke W. A.
collection PubMed
description Intrinsic or added immune activating molecules are key for most vaccines to provide desired immunity profiles but may increase systemic reactogenicity. Regulatory agencies require rabbit pyrogen testing (RPT) for demonstration of vaccine reactogenicity. Recently, the monocyte activation test (MAT) gained popularity as in vitro alternative, yet this assay was primarily designed to test pyrogen-free products. The aim was to adjust the MAT to enable testing of pyrogen containing vaccines in an early stage of development where no reference batch is yet available. The MAT and RPT were compared for assessing unknown safety profiles of pertussis outer membrane vesicle (OMV) vaccine candidates to those of Bexsero as surrogate reference vaccine. Pertussis OMVs with wild-type LPS predominantly activated TLR2 and TLR4 and were more reactogenic than Bexsero. However, this reactogenicity profile for pertussis OMVs could be equalized or drastically reduced compared to Bexsero or a whole-cell pertussis vaccine, respectively by dose changing, modifying the LPS, intranasal administration, or a combination of these. Importantly, except for LPS modified products, reactogenicity profiles obtained with the RPT and MAT were comparable. Overall, we demonstrated that this pertussis OMV vaccine candidate has an acceptable safety profile. Furthermore, the MAT proved its applicability to assess reactogenicity levels of pyrogen containing vaccines at multiple stages of vaccine development and could eventually replace rabbit pyrogen testing.
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spelling pubmed-104035502023-08-06 In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines Molenaar-de Backer, Marijke W. A. Doodeman, Paulien Rezai, Fereshte Verhagen, Lisa M. van der Ark, Arno Plagmeijer, Els M. Metz, Bernard van Vlies, Naomi Ophorst, Olga Raeven, René H. M. Sci Rep Article Intrinsic or added immune activating molecules are key for most vaccines to provide desired immunity profiles but may increase systemic reactogenicity. Regulatory agencies require rabbit pyrogen testing (RPT) for demonstration of vaccine reactogenicity. Recently, the monocyte activation test (MAT) gained popularity as in vitro alternative, yet this assay was primarily designed to test pyrogen-free products. The aim was to adjust the MAT to enable testing of pyrogen containing vaccines in an early stage of development where no reference batch is yet available. The MAT and RPT were compared for assessing unknown safety profiles of pertussis outer membrane vesicle (OMV) vaccine candidates to those of Bexsero as surrogate reference vaccine. Pertussis OMVs with wild-type LPS predominantly activated TLR2 and TLR4 and were more reactogenic than Bexsero. However, this reactogenicity profile for pertussis OMVs could be equalized or drastically reduced compared to Bexsero or a whole-cell pertussis vaccine, respectively by dose changing, modifying the LPS, intranasal administration, or a combination of these. Importantly, except for LPS modified products, reactogenicity profiles obtained with the RPT and MAT were comparable. Overall, we demonstrated that this pertussis OMV vaccine candidate has an acceptable safety profile. Furthermore, the MAT proved its applicability to assess reactogenicity levels of pyrogen containing vaccines at multiple stages of vaccine development and could eventually replace rabbit pyrogen testing. Nature Publishing Group UK 2023-08-04 /pmc/articles/PMC10403550/ /pubmed/37542099 http://dx.doi.org/10.1038/s41598-023-39908-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Molenaar-de Backer, Marijke W. A.
Doodeman, Paulien
Rezai, Fereshte
Verhagen, Lisa M.
van der Ark, Arno
Plagmeijer, Els M.
Metz, Bernard
van Vlies, Naomi
Ophorst, Olga
Raeven, René H. M.
In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
title In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
title_full In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
title_fullStr In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
title_full_unstemmed In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
title_short In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
title_sort in vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403550/
https://www.ncbi.nlm.nih.gov/pubmed/37542099
http://dx.doi.org/10.1038/s41598-023-39908-7
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