Immunization with the Recombinant Surface Protein rTcSP2 Alone or Fused to the CHP or ATPase Domain of TcHSP70 Induces Protection Against Acute Trypanosoma cruzi Infection

Alejandro Carabarin-Lima, Mar&

Abstract

A surface protein (TcSP2) of Trypanosoma cruzi was evaluated alone or fused to the chaperone (CHP) or ATPase (ATP) domains of heat shock protein 70 (TcHSP70) as a vaccine candidate in a murine model for experimental acute T. cruzi infection. BALB/c mice were immunized with the recombinant proteins rTcSP2, TcSP2-CHP, or rTcSP2-ATP and infected with blood trypomastigotes. rTcSP2 and rTcSP2-ATP induced IgG1, IgG2a, and IgG2b isotypes (mixed Th1- Th2), and rTcSp2-CHP induced IgG2b>IgG2a>IgG1 isotypes, with an IgG2b/IgG1 ratio > 1 (Th1). After immunization and parasite challenge, a 75% decrease in parasitemia was detected in mice immunized with rTcSP2 or rTcSP2-CHP, and a 50% decrease was observed with rTcSP2-ATP. Survival was 100% for animals immunized with rTcSP2 and 75% for those immunized with rTcSP2-CHP or rTcSP2-ATP. Before the parasite challenge, the recombinant proteins promoted increased serum levels of cytokines interleukin (IL)-2, IL-10 and interferon (IFN)-γ but not IL-4, indicating a Th1-type cellular immune response; these levels increased after the challenge. Histological staining revealed decreased heart tissue damage and little inflammatory cell infiltrate in animals immunized with rTcSP2. The above result indicates that rTcSP2, alone or fused to the TcHSP70 domains, is a potential candidate for the development of a vaccine against Chagas disease.

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