Use of metalloproteinases thermolysin and leptolysin, and LigA as vaccine candidates against experimental leptospirosis.

• Grant number: 24/16836-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Lourdes Isaac
• Grantee: Daniella dos Santos Courrol
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/12924-3 - Etiopathogenesis of Leptospirosis: contribution of the complement system for the control of infection in vivo and in vitro and inflammatory response: identification of gene polymorphisms of the complement system in Leptospirosis patients, AP.TEM

Abstract

Leptospirosis is a zoonosis caused by spirochete bacteria from the genus Leptospira. It is very common in tropical and subtropical areas and it represents a serious public health problem. Currently, vaccines for leptospirosis show low efficacy, several side effects, a lack of cross-protection for different serovars, and short-term immunity. In studies conducted by our group, it was observed that the metalloproteases thermolysin and leptolysin were capable of degrading proteins from the Complement System and components of the extracellular matrix. The cleavage of these proteins may constitute a new mechanism of immune evasion by Leptospira. Considering this important biological activity and the lack of studies on Leptospira proteases for vaccine formulations, we believe that is highly relevant to evaluate the metalloproteases thermolysin and leptolysin, together with LigA, as potential vaccine candidates. To this end, hamsters and C3H/HeJ mice (TLR4-deficient), both susceptible to infection by pathogenic *Leptospira*, will be immunized with recombinant thermolysin, leptolysin, and LigA, using aluminum hydroxide as an adjuvant, and then challenged with inocula containing pathogenic *Leptospira* L. interrogans serovar FIOCRUZ L1-130, and compared with non-immunized controls. This study aims to investigate the production of specific antibodies and evaluate the level of protection conferred by the prior immunization of these animals before they are challenged with Leptospira.