Evaluation of the immune protective potential of Leptospira interrogans recombinant antigens

A leptospirose ?? uma doen??a causada por espiroquetas do g??nero Leptospira. Ela ?? a zoonose mais difundida no mundo, sendo um problema de sa??de p??blica e veterin??ria, principalmente em pa??ses em desenvolvimento. Na ??rea de veterin??ria, a leptospirose ?? preocupante do ponto de vista cl??nico e econ??mico, devido ao risco ?? sa??de p??blica, perdas reprodutivas e ??bitos. A vacina????o animal ?? amplamente realizada como medida de preven????o da enfermidade. Entretanto, a prote????o conferida pelas vacinas convencionais ?? limitada aos sorovares nelas presentes, n??o evitando o estado portador, mantendo assim o potencial transmissor desses animais, para humanos e outros animais. Por outro lado, vacinas para humanos est??o dispon??veis e empregadas em alguns pa??ses como a China e Cuba. O objetivo deste trabalho foi avaliar, em modelo animal, prote??nas recombinantes de Leptospira interrogans quanto ao seu potencial imunoprotetor. Para tanto, vinte prote??nas foram expressas em Escherichia coli e, ap??s a adsor????o em hidr??xido de alum??nio, foram administradas em hamsters atrav??s da via intramuscular, em duas doses, com intervalo de 14 dias. Duas semanas ap??s a segunda dose realizou-se o desafio dos animais com 100 leptospiras (~2xDL50). Ap??s o desafio, os animais foram observados diariamente para o aparecimento de sinais cl??nicos da enfermidade e ??bitos, e ap??s 24 dias procedeu-se a eutan??sia e necropsia dos animais sobreviventes. Como resultado da avalia????o realizada, sete prote??nas conferiram prote????o ao modelo animal que variou de 16,7% a 50%. Das prote??nas que apresentaram maiores n??veis de prote????o, duas foram indicadas como poss??veis candidatas ?? vacina recombinante contra leptospirose.Leptospirosis is a disease caused by pathogenic spirochetes of the Leptospira genus. It is the most widespread zoonosis in the world, representing a veterinarian and public health problem especially in developing countries. From a veterinarian point of view, leptospirosis is important both as a medical problem, mainly in dogs, which can suffer the ailment as well as transmit it, and as an economic problem, mainly in cattle and pigs, where it causes direct production and reproductive losses. Vaccination of these animals is largely applied, however protection is limited. Conventional vaccines confer protection restricted to the sorovars present in the preparation and fail to protect against renal infection, allowing seemingly healthy animals to shed bacteria, and produce short term protection requiring frequent revaccination. The vaccines are also available for humans, but are used only in a few countries such as Cuba and China. The goal of this work was to test the immune protective potential of recombinant Leptospira interrogans proteins produced in Escherichia coli, using the hamster model. Twenty recombinant vaccine candidates were produced and inoculated in hamsters in two doses, fourteen days apart. Two weeks after the second dose all animals were challenged with 100 leptospires (~2xLD50). After the challenge, animals were observed daily for disease. Of all the proteins tested, seven protected animals to some extent, ranging from 16.7% to 50%. Two proteins presented promising results, and were recommended for further studies, as potential leptospira subunit vaccine candidates