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Evaluation and characterization of vaccine candidates against leptospirosis

Grant number: 12/01797-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): February 29, 2016
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Ana Lucia Tabet Oller do Nascimento
Grantee:Aline Rodrigues Florêncio Teixeira
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Leptospirosis is a worldwide zoonosis regarded as a major public health problem. In Brazil, outbreaks occur mainly in rainfall periods in metropolitan areas that have inadequate infrastructure favoring the proliferation of rodents which are the main reservoirs of the disease. Measures to control the disease are difficult to implement. The development of new strategies to prevent and control the spread of leptospirosis is urgently needed. Accordingly, prophylactic vaccines or immunotherapeutic emerge as a strong candidate to solve the problem. Only Cuba and China have licensed vaccines for humans, but these formulations are based on inactivated leptospires presenting a series of side effects and are serovar-dependent. For this reason, currently research has focused to identify conserved antigens that are involved in host-pathogen interactions. Thus, this project aims to assess the functional properties of three genes (LIC13479, LIC10050 and LIC10537) identified in the genome sequences of Leptospira interrogans serovar Copenhageni. These genes will be amplified from genomic DNA of L. interrogans, and the DNA inserts cloned in appropriate vectors using E. coli as a host expression system. The recombinant proteins will be purified by metal chelating chromatography, analyzed for its structure by the technique of circular dichroism and immunogenicity evaluated in sera of mice immunized with the proteins by ELISA and / or Western blotting. The recombinant proteins will be assessed for their reactivity to extracellular matrix components and to serum components. Moreover, the immunoprotective activity will be assessed in animal model. These experimental steps will be crucial for the identification of novel vaccine candidates.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SIQUEIRA, GABRIELA H.; TEIXEIRA, ALINE F.; FERNANDES, LUIS G.; DE SOUZA, GISELE O.; KIRCHGATTER, KARIN; ROMERO, ELIETE C.; VASCONCELLOS, SILVIO A.; VIEIRA, MONICA L.; NASCIMENTO, ANA LUCIA T. O.. The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans. PATHOGENS AND DISEASE, v. 74, n. 2, . (12/23913-9, 12/01797-7, 12/50523-7, 14/18337-4, 14/03792-8, 12/24164-0)
FERNANDES, LUIS G. V.; TEIXEIRA, ALINE F.; FILHO, ANTONIO F. S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Immune response and protective profile elicited by a multi-epitope chimeric protein derived from Leptospira interrogans. INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, v. 57, p. 61-69, . (12/01797-7, 12/23913-9, 14/50981-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TEIXEIRA, Aline Rodrigues Florêncio. Evaluation and characterization of vaccine candidates against leptospirosis.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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