We have previously shown that immunization of mice with the vaccine candidate, the 28-kDa glutathione-S-transferase of Schistosoma mansoni (Sm28-GST), in alum or complete Freund's adjuvant, or with recombinant Salmonella typhimurium expressing Sm28-GST, induced type 2, mixed, or type 1 immune responses, respectively. In the present study we examined whether the genetic background, the dose and the route of antigen administration could modulate the profile of the immune response induced during these immunizations. Our results show that the nature of the adjuvant is the major factor that determines the profile of the response. Surprisingly, the genetic background did not influence the response, while the route of immunization, and to a lesser extent the dose of the antigen, weakly modulated the adjuvant-dependent orientation of the immune response.