Evaluation and characterization of vaccine candidates against leptospirosis

• Grant number: 12/01797-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2012
• End date: 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

Abstract

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.

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)

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, APR 2017. (12/01797-7, 12/23913-9, 14/50981-0)

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, MAR 2016. (12/23913-9, 12/01797-7, 12/50523-7, 14/18337-4, 14/03792-8, 12/24164-0)

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.