96087 20230921135434.0 doi 10.3390/vaccines8040594 sideral 120751 ART-2020-120751 eng Arenas, J. Universidad de Zaragoza (orcid)0000-0002-8134-0693 Shortening the lipid A acyl chains of Bordetella pertussis enables depletion of lipopolysaccharide endotoxic activity 2020 Access copy available to the general public Unrestricted 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. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.422 2020 MEDICINE, RESEARCH & EXPERIMENTAL 63 / 140 = 0.45 2020 Q2 T2 IMMUNOLOGY 74 / 162 = 0.457 2020 Q2 T2 1.296 2020 Drug Discovery 2020 Q1 Immunology 2020 Q1 Pharmacology (medical) 2020 Q1 Pharmacology 2020 Q1 Infectious Diseases 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Pupo, E. Phielix, C. David, D. Zariri, A. Zamyatina, A. Tommassen, J. van der Ley, P. 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 8, 4 (2020), 594 [20 pp] Vaccines 2076-393X 636229 http://zaguan.unizar.es/record/96087/files/texto_completo.pdf Versión publicada 485549 http://zaguan.unizar.es/record/96087/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:96087 articulos driver 2023-09-21-13:30:51 ARTICLE