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Development of a subunit vaccine against leptospirosis based on LigA e LigB proteins.

Grant number: 15/19445-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2016
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Paulo Lee Ho
Grantee:Denize Monaris
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira which colonize the renal tubules of wild or domestic animals and are released to the external environment in urine. The transmission occurs through accidental contact with water, food and soil contaminated with urine of infected animals. The development of a vaccine is very important, since the control of carrier animals is difficult. Some vaccines are being used, but they promote protection only against the serotypes present in the preparation and fail to induce immunity in the long-term. The LigA and LigB proteins (leptospiral immunoglobulin-like proteins) are characterized by the presence of repeated Big domains. They are located in the outer membrane of bacteria and participate in adhesion processes of leptospires to host tissue cells. They are the most promising vaccine antigens tested to date. Results obtained by several groups have shown that these recombinant proteins were able to induce protection against death caused by leptospirosis. However, the surviving animals were positive during the isolation of leptospires in samples of kidney and liver. In this project, we intend to develop and characterize a subunit vaccine against leptospirosis able to protect against death and able to prevent the colonization of organs. Therefore, the LigA and LigB proteins will be fused to the ZZ domain of protein A from Staphylococcus aureus and/ r R domain of diphtheria toxin and/or the TAT protein of the HIV virus. The vaccine and immunogenic potential of these different formulations will be tested in immunization and challenge studies using model hamsters. It is expected that these molecules contribute to increase the immunogenicity of the LigA and LigB proteins through the increased efficiency of antigen presentation processes to the immune system.