Leptospirose no Brasil: o impacto na saúde pública e o desenvolvimento de novas vacinas

Abstract

Leptospirosis is an infectious disease caused by pathogenic spirochetes of the Leptospira genus, with complications in humans and animals. This disease is transmitted via direct contact with an infected animal or with an environment contaminated with their urine. Rodents can carry leptospires in their renal tubules and are considered the main source of leptospires for new infections. In susceptible hosts, pathogenic leptospires spread throughout the body, resulting in a potentially fatal, severe disease with multiple organ failure. In veterinary medicine, vaccination is the most effective approach for leptospirosis prophylaxis. The bacterins, the only currently available vaccines, induce only a short-term immune response that is serovar-specific. Efforts to develop a new recombinant vaccine as a possible solution to these problems have achieved limited success and the development of vaccines to replace bacterins, remains a challenge. In this study, the current scenario of leptospirosis DNA vaccine development was reviewed and prospective vaccine targets were identified. The lemA and ligBrep genes were shown as promising antigens. These antigens, when used in Prime-boost immunization conferred 87.5% and 83.3% protection, respectively. Furthermore, we report for the first time the evaluation of bacterin, bacterin co-administered with recombinant protein LigBrep and recombinant protein LigBrep as vaccine antigens in long-term experiments. The subunit vaccine preparation, based on LigBrep conferred 50-100% protection against mortality in vaccinated hamsters during the first six months and there was no protection 12 months post-vaccination. Bacterin and bacterin co-administered with recombinant protein LigBrep as antigens conferred 100% of protection in long-term experiments. Moreover, in order to better understand the national impact of the disease, the time trends of the incidence of leptospirosis in Brazil during 2007 to 2014 was performed. During this period, most cases were reported in adult males, however, there was a significant increase in incidence among females, elderly, the children and in the Northern region of the country. Taken together, these findings represent substantial progress for leptospirosis study with impact in public health and development of new vaccines.