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Investigation of metaloprotease papalisina from pathogenic leptospires as vaccine antigen

Grant number: 20/16104-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2021
Effective date (End): July 31, 2022
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal researcher:Lourdes Isaac
Grantee:Isabela Resende Azevedo
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis - a neglected disease of global importance - is caused by pathogenic Leptospira species, once disseminated in the host after the contact with rodent urine, contaminated soil and water by these bacteria. The innate immune system is the first line of defense against microorganisms and the role of the Complement System is of paramount importance to control various types of bacterial infections, such as leptospirosis. However, evasion mechanisms of the Complement System developed by pathogenic leptospires block its activation, favoring the installation of this infection.Nowadays there are no leptospirosis vaccines available for human use that can provide long-lasting and comprehensive protection against different types of leptospiral serovars. As a result, in recent years, several research groups have studied several vaccine candidates to try to solve this gap.Our group previously demonstrated that certain metalloproteases secreted by pathogenic leptospires are capable of cleaving proteins from the Complement System, avoiding their activation. From an exoproteomic analysis of L. interrogans, papalisin - a metallopeptidase conserved in the genome of pathogenic Leptospira species - was identified with a corresponding orthologous form in humans. Unpublished data from the group of Dr. Angela Silva Barbosa (Instituto Butantan) indicate that papalisin is expressed in abundance and capable of cleaving proteins from the Complement System. This project aims to evaluate the use of leptospiral papalisin as a possible vaccine candidate, capable of inducing protection against leptospirosis.

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