Trypanosoma cruzi variants with reduced virulence obtained by mutagenesis

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Abstract
Previous reports have indicated that by mutagen treatment of mouse tumor cells in vitro it is possible to obtain at high frequency stable tumor cell variants that fail to form tumors in syngeneic mice because of increased immunogenicity. By analogy with these tumor cell variants, whether variants with reduced virulence could be obtained by mutagen treatment of trypomastigotes derived from a T. cruzi strain that was adapted to culture and produced lethal infections in DBA/2 mice at a dose of 5 .times. 104 parasites, was investigated. A very large frequency of T. cruzi clones were obtained that failed to provoke an acute lethal infection after injection of 5 .times. 105 parasites. Most of these variants with reduced virulence (vir-) multiplied actively in normal mice until day 8 after injection. After that time the parasitaemia decreased gradually. For most variants a low level of residual parasitemia persisted for > 100 days. Unlike the situation encountered with mouse tumor cell variants it was not possible to demonstrate the presence of new antigens on the T. cruzi vir- variants. These variants seemed to have acquired an increased immunogenicity since they provoked the rejection of virulent parasites injected concomitantly. Mice that were immunized with living vir- clones were protected against a challenge with a virulent clone derived from the original parasite population.