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"evaluation of immunoprotective potential of CD4+ T-cell epitopes identified ín proteins of Leptospira interrogans"

Grant number: 16/11541-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2016
Effective date (End): December 02, 2020
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Ana Lucia Tabet Oller Do Nascimento
Grantee:Aline Rodrigues Florêncio Teixeira
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:14/50981-0 - Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis, AP.TEM
Associated scholarship(s):19/05466-4 - Identification of leptospiral antigens recognized by gamma/delta T cells as target for development of next generation vaccines, BE.EP.PD

Abstract

Leptospirosis is a systemic disease caused by pathogenic bacteria of the genus Leptospira. The disease is considered a worldwide zoonosis and regarded as a major public health problem. It is expected that over 1 million new infections may occur annually. In Brazil, outbreaks occur mainly in rainfall periods in urban settings due to inadequate infrastructure, favoring the proliferation of rodents, which are the main reservoirs of the disease. Public health interventions against leptospirosis need to focus on preventive measures. The development of a vaccine is critical, for there are, at present, no practicable measures to control rodent reservoirs. Only Cuba and China have licensed vaccines for humans, but these formulations are based on inactivated leptospires presenting a series drawbacks, such as serovar-dependence and short-term immunity. The development of new strategies to prevent and control the spread of leptospirosis is urgently needed. Advances in the recombinant DNA technology associated with the genome sequences of Leptospira have contributed to the identification of vaccine candidates. Nevertheless, the use of recombinant proteins as vaccine antigens until now has not shown promising results. The development of protective epitopes-based peptide vaccine emerges as an attractive alternative strategy to solve this problem. These peptide epitopes represent the minimal immunogenic region of a protein antigen and allow for precise direction of immune responses. Based on these expectations, the present project proposes the identification, characterization and evaluation of the vaccine potential of immunodominant epitopes of CD4+ T cells derived from Lsa46 and Lsa77 proteins. Since activation of CD4+ T cells is essential for the development of adaptative immune response, the identification and characterization of these epitopes will contribute to the understanding of how CD4 + T cell responses are involved in the protection of leptospirosis. This should provide useful insights for the development of vaccines against the disease.

Scientific publications (4)
(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)
TEIXEIRA, ALINE F.; FERNANDES, V, LUIS G.; CAVENAGUE, MARIA F.; TAKAHASHI, MARIA B.; SANTOS, JADEMILSON C.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; KOCHI, LEANDRO T.; VIEIRA, MONICA L.; NASCIMENTO, ANA L. T. O. Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines. Vaccine, v. 37, n. 30, p. 3961-3973, JUL 9 2019. Web of Science Citations: 1.
CAVENAGUE, MARIA F.; TEIXEIRA, ALINE F.; FILHO, ANTONIO S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O. Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen, vitronectin and complement binding properties. INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, v. 309, n. 2, p. 116-129, MAR 2019. Web of Science Citations: 2.
NASCIMENTO FILHO, EDSON G.; VIEIRA, MONICA L.; TEIXEIR, ALINE F.; SANTOS, JADEMILSON C.; FERNANDES, LUIS G. V.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; ROSSINI, AMANDA; KOCHI, LEANDRO T.; CAVENAGUE, MARIA F.; PIMENTA, DANIEL C.; NASCIMENTO, ANA L. T. O. Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications. JOURNAL OF PROTEOMICS, v. 180, n. SI, p. 80-87, MAY 30 2018. Web of Science Citations: 1.
TEIXEIRA, ALINE F.; FERNANDES, LUIS G. V.; SOUZA FILHO, ANTONIO; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O. Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis. BIOMED RESEARCH INTERNATIONAL, 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.