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Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity

Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by s...

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Autores principales: Arenas, Jesús, Pupo, Elder, Phielix, Coen, David, Dionne, Zariri, Afshin, Zamyatina, Alla, Tommassen, Jan, van der Ley, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712016/
https://www.ncbi.nlm.nih.gov/pubmed/33050234
http://dx.doi.org/10.3390/vaccines8040594
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author Arenas, Jesús
Pupo, Elder
Phielix, Coen
David, Dionne
Zariri, Afshin
Zamyatina, Alla
Tommassen, Jan
van der Ley, Peter
author_facet Arenas, Jesús
Pupo, Elder
Phielix, Coen
David, Dionne
Zariri, Afshin
Zamyatina, Alla
Tommassen, Jan
van der Ley, Peter
author_sort Arenas, Jesús
collection PubMed
description Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by subunit vaccines around the turn of the century. However, there is a considerable increase in the number of cases in industrialized countries. A possible strategy to improve vaccine-induced protection is the development of new, non-toxic, whole-cell pertussis vaccines. The reactogenicity of whole-cell pertussis vaccines is, to a large extent, derived from the lipid A moiety of the lipopolysaccharides (LPS) of the bacteria. Here, we engineered B. pertussis strains with altered lipid A structures by expressing genes for the acyltransferases LpxA, LpxD, and LpxL from other bacteria resulting in altered acyl-chain length at various positions. Whole cells and extracted LPS from the strains with shorter acyl chains showed reduced or no activation of the human Toll-like receptor 4 in HEK-Blue reporter cells, whilst a longer acyl chain increased activation. Pyrogenicity studies in rabbits confirmed the in vitro assays. These findings pave the way for the development of a new generation of whole-cell pertussis vaccines with acceptable side effects.
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spelling pubmed-77120162020-12-04 Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity Arenas, Jesús Pupo, Elder Phielix, Coen David, Dionne Zariri, Afshin Zamyatina, Alla Tommassen, Jan van der Ley, Peter Vaccines (Basel) Article Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by subunit vaccines around the turn of the century. However, there is a considerable increase in the number of cases in industrialized countries. A possible strategy to improve vaccine-induced protection is the development of new, non-toxic, whole-cell pertussis vaccines. The reactogenicity of whole-cell pertussis vaccines is, to a large extent, derived from the lipid A moiety of the lipopolysaccharides (LPS) of the bacteria. Here, we engineered B. pertussis strains with altered lipid A structures by expressing genes for the acyltransferases LpxA, LpxD, and LpxL from other bacteria resulting in altered acyl-chain length at various positions. Whole cells and extracted LPS from the strains with shorter acyl chains showed reduced or no activation of the human Toll-like receptor 4 in HEK-Blue reporter cells, whilst a longer acyl chain increased activation. Pyrogenicity studies in rabbits confirmed the in vitro assays. These findings pave the way for the development of a new generation of whole-cell pertussis vaccines with acceptable side effects. MDPI 2020-10-09 /pmc/articles/PMC7712016/ /pubmed/33050234 http://dx.doi.org/10.3390/vaccines8040594 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arenas, Jesús
Pupo, Elder
Phielix, Coen
David, Dionne
Zariri, Afshin
Zamyatina, Alla
Tommassen, Jan
van der Ley, Peter
Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity
title Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity
title_full Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity
title_fullStr Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity
title_full_unstemmed Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity
title_short Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity
title_sort shortening the lipid a acyl chains of bordetella pertussis enables depletion of lipopolysaccharide endotoxic activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712016/
https://www.ncbi.nlm.nih.gov/pubmed/33050234
http://dx.doi.org/10.3390/vaccines8040594
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