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Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines

Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intr...

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Autores principales: Carson, Danielle, Myhill, Sophie, Palmieri, Elena, Necchi, Francesca, Rijpkema, Sjoerd, Micoli, Francesca, Nordgren, Ida Karin, Rossi, Omar, Vipond, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306433/
https://www.ncbi.nlm.nih.gov/pubmed/34202832
http://dx.doi.org/10.3390/microorganisms9071375
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author Carson, Danielle
Myhill, Sophie
Palmieri, Elena
Necchi, Francesca
Rijpkema, Sjoerd
Micoli, Francesca
Nordgren, Ida Karin
Rossi, Omar
Vipond, Caroline
author_facet Carson, Danielle
Myhill, Sophie
Palmieri, Elena
Necchi, Francesca
Rijpkema, Sjoerd
Micoli, Francesca
Nordgren, Ida Karin
Rossi, Omar
Vipond, Caroline
author_sort Carson, Danielle
collection PubMed
description Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of Shigella GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A–C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component Shigella GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release.
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spelling pubmed-83064332021-07-25 Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines Carson, Danielle Myhill, Sophie Palmieri, Elena Necchi, Francesca Rijpkema, Sjoerd Micoli, Francesca Nordgren, Ida Karin Rossi, Omar Vipond, Caroline Microorganisms Article Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of Shigella GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A–C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component Shigella GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release. MDPI 2021-06-24 /pmc/articles/PMC8306433/ /pubmed/34202832 http://dx.doi.org/10.3390/microorganisms9071375 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Carson, Danielle
Myhill, Sophie
Palmieri, Elena
Necchi, Francesca
Rijpkema, Sjoerd
Micoli, Francesca
Nordgren, Ida Karin
Rossi, Omar
Vipond, Caroline
Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
title Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
title_full Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
title_fullStr Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
title_full_unstemmed Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
title_short Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
title_sort development of a monocyte activation test as an alternative to the rabbit pyrogen test for mono- and multi-component shigella gmma-based vaccines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306433/
https://www.ncbi.nlm.nih.gov/pubmed/34202832
http://dx.doi.org/10.3390/microorganisms9071375
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