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Evaluation of new vaccine strategies against leptospirosis.


Leptospirosis is a neglected emerging disease which presents broad geographical distribution and great impact on public health and agriculture economy. It is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that colonize the renal tubules of domestic and wild animals and are released to the external environment in urine. The transmission occurs through direct contact with tissues, body fluids and urine of infected animals, or by exposure to contaminated water or soil.The available commercial vaccines consist of leptospiral cultures of different serovars preparations inactivated by the action of heat and/or formaldehyde (bacterins). They are widely used in livestock and licensed for human use in some countries, but promote protection only against the serovars present in the preparation and fail to induce long-term immunity, which requires annual or biannual administration. LigA protein is the most promising vaccine antigen tested to date. Results obtained by several groups have shown that this recombinant protein is 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 intended to develop a subunit leptospiral vaccine, for human and veterinary use, able to protect against death and able to prevent colonization of organs. Therefore, the LigA protein will be fused to the ZZ domain of protein A from S. aureus, and/or R domain of diphtheria toxin and/or the TAT protein of the HIV virus. It is expected that these molecules contribute to increase the immunogenicity of the LigA protein through the increased efficiency of antigen presentation processes of the immune system (AU)