The first DNA vaccines to be tested against T. cruzi encoded an antigen from the well characterized trans-sialidase family of proteins. There are over 1400 members in this family, making it one of the largest protein families of the parasite, and they are very abundant surface proteins. Several studies have used different members of this family, such as TS or TSA-1 (Table 3 ) [84, [86] [87] [88] . Immunization with TS was found to induce significant antibody titers able to inhibit trans-sialidase enzyme activity, a strong DTH, and lymphoproliferative response [86] . This immune response was protective as determined by an increase in survival and a decrease in parasitemia. Immunization with TSA-1 DNA was found to induce a specific CTL response which also lead to a lower parasitemia and increased survival in both BALB/c and C57BL/6 mice [88] . As in Leishmania vaccine studies, a few authors addressed the question of comparing protein and DNA vaccines encoding the same antigen [90, 98] . In A/Sn mice, immunization with recombinant TS induced a higher antibody titer than TS DNA, but a comparable decrease in parasitemia. However, the DNA vaccine was unable to increase survival, which the author attributed to the strain of the mice used, since this DNA vaccine was protective in BALB/c mice [90] . On the other hand, immunization with recombinant CRP or CRP DNA induced a comparable Th1 immune response, but only the DNA vaccine was protective against infection [98] .