Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes.

FRANK FM, PETRAY PB, CAZORLA SI, MUÑOZ MC, CORRAL RS, MALCHIODI EL.

VACCINE

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2003 vol. 22 p. 77 - 86

0264-410X

The crucial role played by Ag163B6/cruzipain, the major cystein proteinase ofTrypanosoma cruzi, in the process of parasite internalization into mammaliancells and IgG hydrolysis, signals this antigen as a potential target for raising a protective immune response against Chagas´ disease. On the other hand,synthetic oligodeoxynucleotides containing CpG-motifs (CpG-ODN) are capable ofdriving immunity toward a Th1 bias. Considering the importance of Th1 mechanisms in resistance against this intracellular parasite, we analyzed the ability ofAg163B6/cruzipain plus CpG-ODN to induce immunoprotection against a lethalchallenge with trypomastigotes. Mice were immunized with Ag163B6+CpG-ODN showing high specific antibody titers, mostly IgG2a. Spleen cells from these micestrongly proliferated and presented significant increase of IL-2 and IFN-gammaconcentrations in their supernatant upon antigen stimulation. Trypomastigotechallenge rendered elevated parasitemia and mortality in all control groups,meanwhile Ag163B6+CpG-ODN mice displayed the lowest level of blood parasites and 100% survival to acute infection. Besides, we demonstrated that other parasiteantigens introduced into mice when challenged, and consequently never seen beforeby the immune system, also elicited a Th1 immune response. Taken together, these results plus others provide the basis for the design of a multicomponent anti-T. cruzi vaccine which may ultimately be used not only to protect humans at risk of infection, but also may alleviate or prevent the pathogenic responsescharacteristic of chronic Chagas´ disease by reducing or perhaps eliminatingtissue parasites from infected patients.