Mitomycin C-treated Trypanosoma cruzi in vaccination of mice: induction of immunosuppression but not protection

Abstract

Attempts to immunize susceptible hosts against infection with Trypanosoma cruzi have generally not met with a high degree of success. In the present study, we used the antimetabolite mitomycin C to produce nonreplicating, attenuated culture forms of T. cruzi. Attempts to immunize highly susceptible C3H(He) mice with single or multiple inoculi of mitomycin C-treated trypanosomes 2 weeks before injection of infective blood-form trypomastigotes did not, however, lead to greater longevity in immunized mice over nonimmunized, control mice. It was determined that a single injection of 10(7) attenuated parasites induced a transient suppression of the immune response to sheep erythrocytes which was maximum on day 7, less on day 14, and undetectable by the 21st day after immunization. This immunosuppression to a heterologous antigen did not, however, appear to be the cause of the failure of the vaccination procedure to elicit protective immunity since mice immunized once with 10(7) mitomycin C-treated trypanosomes and challenged 30, 60, or 90 days later exhibited no greater longevity than control mice.