As for any vaccine, the nature of the antigen used remains a key factor for vaccine efficacy, and there is still little variety in terms of antigens evaluated as DNA vaccine candidates against T. cruzi. Thus, a number of studies have aimed at identifying novel antigens through various strategies. The most classical approach has been the screening of cDNA libraries using antibodies and screening an amastigote library allowed the identification of a novel antigen Tcβ3, and two previously characterized ones, LYT1 and FcaBP/Tc24 [96] . DNA vaccines encoding these antigens induced variable levels of protection, the best one being LYT [96] . Alternatively, expression-library immunization, described above for Leishmania, was also tested with T. cruzi, and found to be immunogenic, but there was no attempt at fractionating the library or identifying protective antigens [107] . A likely reason is that such strategy may be too labor-intensive for large genomes/libraries, and its usefulness may be limited to pathogens with small genomes. The availability of T. cruzi genome sequence also opens new possibilities for antigen discovery. In one of the first studies using such resource, a combination of bioinformatics analysis were used to identify GPI-anchored or secreted proteins, and most of the identified clones were immunogenic as DNA vaccines [108] . Further studies may confirm the usefulness of these new vaccines to protect against T. cruzi infection. Nonetheless, as discussed above for Leishmania, the rationale for limiting antigen searches to surface proteins may not be totally relevant, and additional strategies should also be used to include unbiaised genome-wide surveys for antigen discovery.