Avaliação da eficiência de vacinas de DNA contendo as sequências das proteínas Sm29 e a TSP-2 de Schistosoma mansoni em modelo murino

Abstract

Schistosomiasis is an important parasitic disease worldwide affecting more than 207 million people in 76 countries around the world and causing about 250.000 deaths per year. Nowadays, the main strategy adopted for the control of schistosomiais is the use of safe chemotherapy, as the use of praziquantel. However, the high rates of reinfection after the treatment restrict it as a strategy and assume the need for other forms of control like basic sanitation and vaccination. Because the ability to generate humoral and cellular immune response of DNA vaccines, such strategy is considered to be a promising approach against schistosomiasis. Sm29 and tetraspanin-2 are two proteins localized in S. mansoni tegument of adult worms and schistosomula, with high levels of protection achieved by the recombinant protein approach of immunization, what render them as powerful vaccine candidates. In this work we aim to create, optimize and evaluate in a murine model DNA vaccines carrying such genes, alone or together. By western blot and rt-PCR assessments, we confirm that our DNA vaccines presented the capacity to be transcribed and translated in BHK-21 cells. After immunization, we evaluate the number of worms reduction, We achieved 17%, 21,9% 31% and 24% on animals immunized with the plasmids pUMVC3/Sm29, pUMVC3/TSP-2, pUMVC3/Quimera e pUMVC3/Sm29 + pUMVC3/TSP-2, respectively. No significant difference was achieved in the count of eggs in liver. When the profile of the immunological response was evaluated, we found high production of Th1 cytokines such TNF- and IFN-, and no significant production of IL-4 and IL-5. When measured the levels of anti-Sm29 in serum of immunized mice, no significant production was perceived. Hence, our DNA vaccines showed the ability to generate a protective immune response against schistosomiasis, probably by the production of Th1 cytokines, however, future strategies aiming to optimize the response need to be performed.