• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Thèse de Doctorat
DOI
10.11606/T.10.2016.tde-19082015-155341
Document
Auteur
Nom complet
Denize Monaris
Adresse Mail
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2015
Directeur
Titre en portugais
Avaliação do potencial imunogênico e vacinal das flagelinas de Leptospira interrogans sorovar Copenhageni
Resumé en portugais
A leptospirose é uma zoonose de importância global causada por leptospiras patogênicas, que colonizam os túbulos renais de animais selvagens e domésticos. Vacinas comerciais estão sendo usadas, porém promovem proteção apenas contra os sorovares presentes na preparação e falham em induzir imunidade de longa duração. A porção carboxi-terminal da proteina immunoglobulin like A (LigAC) é capaz de induzir imunoproteção contra a leptospirose. No entanto, a imunização com a LigAC não confere imunidade esterilizante. Flagelinas têm sido consideradas adjuvante promissor para o desenvolvimento de vacinas. As leptospiras possuem dois flagelos periplasmáticos que são constituídos por duas classes de proteínas (FlaA e FlaB). Somente as proteínas FlaB apresentam homologia com as regiões importantes que ativam as respostas dependentes ao receptor Toll-like 5 (TLR-5). Neste estudo, avaliou-se a capacidade de indução da atividade do TLR5 das cinco flagelinas de L. interrogans sorovar Copenhageni (FlaB1, FlaB2, FlaB3, FlaB4 e FlaB5) e o potencial vacinal destas flagelinas na imunidade protetora de LigAC contra o desafio letal em hamsters. As flagelinas recombinantes foram expressas em E. coli e purificadas por cromatografia de afinidade com níquel. Os hamsters foram imunizados por via subcutânea com as flagelinas purificadas e LigAC. Dados experimentais demonstram que todas as flagelinas foram capazes de ativar o receptor TLR5 e a secreção de citocinas em macrógafos estimulados de maneira similar. Nos ensaios de desafio, a maioria dos animais imunizados com as flagelinas e LigAC sobreviveram ao desafio letal entretanto, não foram protegidos contra a colonização renal. Os animais do grupo controle vacinados com PBS morreram com sintomas de leptospirose e hamsters imunizados com a vacina comercial sobreviveram após o desafio
Titre en anglais
Evaluation of the immunogenic potential of flagellins Leptospira like adjuvant for development of a subunit vaccine against leptospirosis
Resumé en anglais
Leptospirosis is a zoonosis of global importance caused by pathogenic leptospires that colonize the renal tubules of wild and domestic animals. Commercial vaccines are being used, but only to promote protection against the serovar in the preparation; they have failed to induce short-term immunity. The C-terminal portion of immunoglobulin-like protein A (LigAC) is able to induce immunoprotection against leptospirosis. However, immunization with LigAC did not confer sterilizing immunity. Flagellins have been considered a promising adjuvant for vaccine development. Leptospires have two periplasmic flagella that are formed by two classes of proteins (FlaA and FlaB); only FlaB proteins show homology with important regions that elicit TLR5-dependent responses. In the present study, we have evaluated their ability to induce the TLR5 activity and the protective activity of five L. interrogans sorovar Copenhageni flagellins (FlaB1, FlaB2, FlaB3, FlaB4 and FlaB5) in the protective immunity of LigAC against lethal challenge in hamsters. The recombinant flagellins expressed in E.coli were purified by nickel affinity chromatography. Hamsters were immunized subcutaneously with purified flagellins with LigAC. Experimental data showed that all flagellins activated both the TLR-5 receptor and the secretion of cytokines in stimulated macrofages, similarly. In challenge assays, the majority of hamsters immunized with the flagellins and LigAC survived the lethal challenge. However, they were not protected against kidney colonization. The control animals vaccinated with PBS died with symptoms of leptospirosis and hamsters vaccinated with commercial vaccine survived after challenge
 
Date de Publication
2016-04-07
 
Tous droits de la thèse/dissertation appartiennent aux auteurs
CeTI-SC/STI
Bibliothèque Numérique de Thèses et Mémoires de l'USP. Copyright © 2001-2022. Tous droits réservés.