<i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity

One of the main virulence factors produced by <i>Bordetella pertussis</i> is pertussis toxin (PTx) which, in its inactivated form, is the major component of all marketed acellular pertussis vaccines. PTx ADP ribosylates Gα<sub>i</sub> proteins, thereby affecting the inhibitio...

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Main Author: Marieke Esther Hoonakker
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/13/8/565
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author Marieke Esther Hoonakker
author_facet Marieke Esther Hoonakker
author_sort Marieke Esther Hoonakker
collection DOAJ
description One of the main virulence factors produced by <i>Bordetella pertussis</i> is pertussis toxin (PTx) which, in its inactivated form, is the major component of all marketed acellular pertussis vaccines. PTx ADP ribosylates Gα<sub>i</sub> proteins, thereby affecting the inhibition of adenylate cyclases and resulting in the accumulation of cAMP. Apart from this classical model, PTx also activates some receptors and can affect various ADP ribosylation- and adenylate cyclase-independent signalling pathways. Due to its potent ADP-ribosylation properties, PTx has been used in many research areas. Initially the research primarily focussed on the <i>in vivo</i> effects of the toxin, including histamine sensitization, insulin secretion and leukocytosis. Nowadays, PTx is also used in toxicology research, cell signalling, research involving the blood–brain barrier, and testing of neutralizing antibodies. However, the most important area of use is testing of acellular pertussis vaccines for the presence of residual PTx. <i>In vivo</i> models and <i>in vitro</i> assays for PTx often reflect one of the toxin’s properties or details of its mechanism. Here, the established and novel <i>in vivo</i> and <i>in vitro</i> methods used to evaluate PTx are reviewed, their mechanisms, characteristics and limitations are described, and their application for regulatory and research purposes are considered.
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spelling doaj.art-1f76b65269944e578cc089a4c5737cb62023-11-22T10:04:48ZengMDPI AGToxins2072-66512021-08-0113856510.3390/toxins13080565<i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin ActivityMarieke Esther Hoonakker0Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The NetherlandsOne of the main virulence factors produced by <i>Bordetella pertussis</i> is pertussis toxin (PTx) which, in its inactivated form, is the major component of all marketed acellular pertussis vaccines. PTx ADP ribosylates Gα<sub>i</sub> proteins, thereby affecting the inhibition of adenylate cyclases and resulting in the accumulation of cAMP. Apart from this classical model, PTx also activates some receptors and can affect various ADP ribosylation- and adenylate cyclase-independent signalling pathways. Due to its potent ADP-ribosylation properties, PTx has been used in many research areas. Initially the research primarily focussed on the <i>in vivo</i> effects of the toxin, including histamine sensitization, insulin secretion and leukocytosis. Nowadays, PTx is also used in toxicology research, cell signalling, research involving the blood–brain barrier, and testing of neutralizing antibodies. However, the most important area of use is testing of acellular pertussis vaccines for the presence of residual PTx. <i>In vivo</i> models and <i>in vitro</i> assays for PTx often reflect one of the toxin’s properties or details of its mechanism. Here, the established and novel <i>in vivo</i> and <i>in vitro</i> methods used to evaluate PTx are reviewed, their mechanisms, characteristics and limitations are described, and their application for regulatory and research purposes are considered.https://www.mdpi.com/2072-6651/13/8/565pertussis toxinacellular pertussis vaccines<i>in vitro</i> assays<i>in vivo</i> models
spellingShingle Marieke Esther Hoonakker
<i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity
Toxins
pertussis toxin
acellular pertussis vaccines
<i>in vitro</i> assays
<i>in vivo</i> models
title <i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity
title_full <i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity
title_fullStr <i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity
title_full_unstemmed <i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity
title_short <i>In Vivo</i> Models and <i>In Vitro</i> Assays for the Assessment of Pertussis Toxin Activity
title_sort i in vivo i models and i in vitro i assays for the assessment of pertussis toxin activity
topic pertussis toxin
acellular pertussis vaccines
<i>in vitro</i> assays
<i>in vivo</i> models
url https://www.mdpi.com/2072-6651/13/8/565
work_keys_str_mv AT mariekeestherhoonakker iinvivoimodelsandiinvitroiassaysfortheassessmentofpertussistoxinactivity