RecombinantMycobacterium bovisBCG is a promising platform to develop vaccines againstTrypansoma cruziinfection

摘要

Chagas disease, caused by the hemoflagelate parasiteTrypanosoma cruzi, is one of the most prevalent endemic parasitoses, affecting 7-8 million people. Due to the complexity of the infection, no vaccines are available at present. The extraordinary adjuvant capacity of bacille Calmette-Guerin (BCG) was explored in this work to develop a vaccine candidate to protect againstT. cruziinfection using the recombinant BCG (rBCG) vaccine platform. Three antigens of the parasite corresponding to the N and C terminal fragments of the enzyme trans-sialidase (NT-TS and CT-TS, respectively) and a fragment of the cruzipain enzyme (CZf) were cloned into the vectors pUS997 and pUS2000 and transformed into the BCG Pasteur strain. In vaccinated mice, rBCG expressing NT-TS in pUS2000 plasmid provided the highest protection and the lowest parasitemia after challenging BALB/c mice with a 50% lethal dose of parasites. When mice vaccinated with pUS2000-NT-TS were challenged with a 100% lethal dose of parasite, high levels of protection were also obtained, together with a low degree of cardiac lesions 120 days after infection. In immunized mice with pUS2000-NT-TS/rBCG clone, the proliferation of CD4(+)cells from splenocytes stimulated with the TS antigen was significant; this stimulation increased interferon (IFN)-gamma and interleukin (IL)-17 within CD4 & x207a; T lymphocytes (LTCD4(+)) cells and IFN-gamma and CD107 expression within LTCD8(+)cells. Therefore, pUS2000-NT-TS/rBCG conferred high levels of protection, which correlated with an immune response orientated towards a T helper type 1 (Th1)/Th17 profile, together with an LTC-specific response, indicating that rBCG is a promising platform to develop vaccines againstT. cruzi.