Evaluation of the vaccine potential of thermolysin from Leptospira interrogans

• Grant number: 14/23983-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2015
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Tatiana Rodrigues Fraga
• Grantee: Jessica Moreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is a widespread zoonosis that represents a serious public health problem. Pathogenic microorganisms, especially those who reach the bloodstream as leptospira, developed multiple strategies to evade the host immune system, in particular the complement system. We recently demonstrated that proteins secreted by pathogenic Leptospira species are able to inhibit all three activation pathways of the human complement system. In addition, we identified a protease of the thermolysin class as one of the responsible for the effects observed in the total supernatant. Considering this important biological activity, we believe that the evaluation of the vaccine potential of this thermolysin is of great relevance, therefore, this is the aim of this project. We are going to use the experimental model of hamsters, which are susceptible to Leptospira infection. Animals will be immunized with the recombinant thermolysin using aluminum hydroxide as adjuvant. Controls groups will be injected with PBS and aluminum hydroxide or the commercial vaccine (FarrowsureB, Pfizer). The animals will be bled from the retro-orbital plexus to assess the titer of anti-thermolysin antibodies. After the immunizations the animals will be challenged with virulent L. interrogans serovar Kennewiki. The hamsters who survived the infection will be sacrificed and the organs collected to perform different analysis, such as histological and leptospiral culture. The identification of potential vaccine candidates for leptospirosis is of great importance and may contribute to the development of preventive strategies in leptospirosis.