Vaccinal evaluation and biochemical caracterization of thermolysin of Leptospira interrogans

• Grant number: 15/09972-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2015
• End date: October 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Lourdes Isaac
• Grantee: Lourdes Isaac
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo

Abstract

Leptospirosis is an important worldwide zoonosis and a public health issue. Some microorganisms developed multiple strategies to escape from the immune system. Pathogenic leptospirosis acquired immune evasion mechanisms, especially to escape from the complement system. Recently, we demonstrated that proteins secreted by pathogenic leptospires are able to inhibit the activation of the complement system. In addition, we identified in the culture supernatants a protease called termolysin, able to cleave certain complement proteins. Considering that, we believe that is very important to evaluate the vaccinal potential of thermolysin and characterize this enzyme (Sub-project 1). We will immunize hamsters with thermolysin using alumen hydroxide and challenge them later with pathogenic leptospire suspensions. The positive control will be formed by hamsters treated with a commercial vaccine (FarrowsureB, Pfizer) and another group will be treated only with PBS in the adjuvant. Blood samples will be withdrawn to monitor the production of anti-thermolysin antibodies. Histopathological analysis and bacterial load will be determined in the survived animals. We will also explore the cleavage of membrane attack complex proteins (C5b, C6, C7, C8 e C9) by thermolysin and culture supernatants of several species of pathogenic leptospires (Sub-project 2). (AU)

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)

DANTAS BREDA, LEANDRO CARVALHO; VASCONCELLOS, SILVIO ARRUDA; VASCONCELOS, DEWTON DE MORAES; ISAAC, LOURDES. Binding of human complement C1 sterase inhibitor to Leptospira spp.. Immunobiology, v. 223, n. 2, p. 183-190, FEB 2018. (11/14347-7, 15/09972-0)

AMAMURA, THAIS A.; FRAGA, TATIANA R.; VASCONCELLOS, SLVIO A.; BARBOSA, ANGELA S.; ISAAC, LOURDES. Pathogenic Leptospira Secreted Proteases Target the Membrane Attack Complex: A Potential Role for Thermolysin in Complement Inhibition. FRONTIERS IN MICROBIOLOGY, v. 8, MAY 30 2017. (15/09972-0)

DE CASTRO, IRIS A.; BAVIA, LORENA; FRAGA, TATIANA R.; AMANO, MARIANE T.; BREDA, LEANDRO C. D.; GRANADOS-MARTINEZ, ADRIANA P.; DA SILVA, ANA M. G.; VASCONCELLOS, SILVIO A.; ISAAC, LOURDES. Role of Murine Complement Component C5 in Acute in Vivo Infection by Pathogenic Leptospira interrogans. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, MAR 8 2018. (15/09972-0, 10/50043-0)

CASTIBLANCO-VALENCIA, MONICA M.; FRAGA, TATIANA R.; BREDA, LEANDRO C. D.; VASCONCELLOS, SILVIO A.; FIGUEIRA, CLAUDIO P.; PICARDEAU, MATHIEU; WUNDER, ELSIO; KO, ALBERT I.; BARBOSA, ANGELA S.; ISAAC, LOURDES. Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum. Immunology Letters, v. 173, p. 61-68, MAY 2016. (15/09972-0, 10/50043-0)