000096087 001__ 96087
000096087 005__ 20230921135434.0
000096087 0247_ $$2doi$$a10.3390/vaccines8040594
000096087 0248_ $$2sideral$$a120751
000096087 037__ $$aART-2020-120751
000096087 041__ $$aeng
000096087 100__ $$0(orcid)0000-0002-8134-0693$$aArenas, J.$$uUniversidad de Zaragoza
000096087 245__ $$aShortening the lipid A acyl chains of Bordetella pertussis enables depletion of lipopolysaccharide endotoxic activity
000096087 260__ $$c2020
000096087 5060_ $$aAccess copy available to the general public$$fUnrestricted
000096087 5203_ $$aWhooping 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.
000096087 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000096087 590__ $$a4.422$$b2020
000096087 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b63 / 140 = 0.45$$c2020$$dQ2$$eT2
000096087 591__ $$aIMMUNOLOGY$$b74 / 162 = 0.457$$c2020$$dQ2$$eT2
000096087 592__ $$a1.296$$b2020
000096087 593__ $$aDrug Discovery$$c2020$$dQ1
000096087 593__ $$aImmunology$$c2020$$dQ1
000096087 593__ $$aPharmacology (medical)$$c2020$$dQ1
000096087 593__ $$aPharmacology$$c2020$$dQ1
000096087 593__ $$aInfectious Diseases$$c2020$$dQ1
000096087 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000096087 700__ $$aPupo, E.
000096087 700__ $$aPhielix, C.
000096087 700__ $$aDavid, D.
000096087 700__ $$aZariri, A.
000096087 700__ $$aZamyatina, A.
000096087 700__ $$aTommassen, J.
000096087 700__ $$avan der Ley, P.
000096087 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000096087 773__ $$g8, 4 (2020), 594 [20 pp]$$tVaccines$$x2076-393X
000096087 8564_ $$s636229$$uhttps://zaguan.unizar.es/record/96087/files/texto_completo.pdf$$yVersión publicada
000096087 8564_ $$s485549$$uhttps://zaguan.unizar.es/record/96087/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000096087 909CO $$ooai:zaguan.unizar.es:96087$$particulos$$pdriver
000096087 951__ $$a2023-09-21-13:30:51
000096087 980__ $$aARTICLE