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| Author(s): |
Denize Monaris
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) |
| Defense date: | 2015-05-06 |
| Examining board members: |
Patricia Antonia Estima Abreu de Aniz;
Anita Mitico Tanaka Azevedo;
Paulo Eduardo Brandão;
Marcia Regina Franzolin;
Andrea Micke Moreno
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| Advisor: | Patricia Antonia Estima Abreu de Aniz |
| Abstract | |
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 (AU) | |
| FAPESP's process: | 10/20525-2 - Evaluation of immunogenic and vaccine potential of Leptospira interrogans sorovar Copenhageni flagellins. |
| Grantee: | Denize Monaris |
| Support Opportunities: | Scholarships in Brazil - Doctorate |