Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in Bordetella pertussis Vaccines

The antigens for acellular pertussis vaccines are made up of protein components that are purified directly from Bordetella pertussis (B. pertussis) bacterial fermentation. As such, there are additional B. pertussis toxins that must be monitored as residuals duri...

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Autores principales:	Lisa Szymkowicz, Jeffery Gerard, Benjamin Messham, Wai Wan Vivian Tam, D. Andrew James
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Bordetella pertussis</i> adenylate cyclase toxin dermonecrotic toxin tracheal cytotoxin pertussis toxin quantitative LC-MS Medicine R
Acceso en línea:	https://doaj.org/article/cc2c323c6ae141afa35d9bbd31203796
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spelling	oai:doaj.org-article:cc2c323c6ae141afa35d9bbd312037962021-11-25T19:08:38ZDesign of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines10.3390/toxins131107632072-6651https://doaj.org/article/cc2c323c6ae141afa35d9bbd312037962021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/763https://doaj.org/toc/2072-6651The antigens for acellular pertussis vaccines are made up of protein components that are purified directly from <i>Bordetella pertussis (B. pertussis)</i> bacterial fermentation. As such, there are additional <i>B. pertussis</i> toxins that must be monitored as residuals during process optimization. This paper describes a liquid chromatography mass spectrometry (LC-MS) method for simultaneous analysis of residual protein toxins adenylate cyclase toxin (ACT) and dermonecrotic toxin (DNT), as well as a small molecule glycopeptide, tracheal cytotoxin (TCT) in a Pertussis toxin vaccine antigen. A targeted LC-MS technique called multiple reaction monitoring (MRM) is used for quantitation of ACT and TCT, which have established limits in drug product formulations. However, DNT is currently monitored in an animal test, which does not have an established quantitative threshold. New approaches for DNT testing are discussed, including a novel standard based on concatenated quantitation sequences for ACT and DNT. Collectively, the method represents a “3-in-1” analytical simplification for monitoring process-related residuals during development of <i>B. pertussis</i> vaccines.Lisa SzymkowiczJeffery GerardBenjamin MesshamWai Wan Vivian TamD. Andrew JamesMDPI AGarticle<i>Bordetella pertussis</i>adenylate cyclase toxindermonecrotic toxintracheal cytotoxinpertussis toxinquantitative LC-MSMedicineRENToxins, Vol 13, Iss 763, p 763 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Bordetella pertussis</i> adenylate cyclase toxin dermonecrotic toxin tracheal cytotoxin pertussis toxin quantitative LC-MS Medicine R
spellingShingle	<i>Bordetella pertussis</i> adenylate cyclase toxin dermonecrotic toxin tracheal cytotoxin pertussis toxin quantitative LC-MS Medicine R Lisa Szymkowicz Jeffery Gerard Benjamin Messham Wai Wan Vivian Tam D. Andrew James Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines
description	The antigens for acellular pertussis vaccines are made up of protein components that are purified directly from <i>Bordetella pertussis (B. pertussis)</i> bacterial fermentation. As such, there are additional <i>B. pertussis</i> toxins that must be monitored as residuals during process optimization. This paper describes a liquid chromatography mass spectrometry (LC-MS) method for simultaneous analysis of residual protein toxins adenylate cyclase toxin (ACT) and dermonecrotic toxin (DNT), as well as a small molecule glycopeptide, tracheal cytotoxin (TCT) in a Pertussis toxin vaccine antigen. A targeted LC-MS technique called multiple reaction monitoring (MRM) is used for quantitation of ACT and TCT, which have established limits in drug product formulations. However, DNT is currently monitored in an animal test, which does not have an established quantitative threshold. New approaches for DNT testing are discussed, including a novel standard based on concatenated quantitation sequences for ACT and DNT. Collectively, the method represents a “3-in-1” analytical simplification for monitoring process-related residuals during development of <i>B. pertussis</i> vaccines.
format	article
author	Lisa Szymkowicz Jeffery Gerard Benjamin Messham Wai Wan Vivian Tam D. Andrew James
author_facet	Lisa Szymkowicz Jeffery Gerard Benjamin Messham Wai Wan Vivian Tam D. Andrew James
author_sort	Lisa Szymkowicz
title	Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines
title_short	Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines
title_full	Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines
title_fullStr	Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines
title_full_unstemmed	Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines
title_sort	design of a quantitative lc-ms method for residual toxins adenylate cyclase toxin (act), dermonecrotic toxin (dnt) and tracheal cytotoxin (tct) in <em>bordetella pertussis</em> vaccines
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cc2c323c6ae141afa35d9bbd31203796
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Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in <em>Bordetella pertussis</em> Vaccines

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