Comparison of antibody and protective immune responses against Trypanosoma cruzi infection elicited by immunization with a parasite antigen delivered as naked DNA or recombinant protein

Abstract

Immunization with naked DNA represents an attractive strategy for development of vaccines against a variety of infections including those caused by protozoan parasites. Recently, we have described that immunization with a plasmid containing the trans-sialidase (TS) gene induced protective immunity against Trypanosoma cruzi infection in BALB/c mice. The present study was aimed at examining and comparing the effectiveness of immunization using either plasmid or recombinant delivered antigens in a mouse strain highly susceptible to infection (A/Sn). Two plasmids were generated containing the coding region for the catalytic domain of TS. TS gene was inserted into pcDNA3 vector with or without the coding region for TS signal peptide. These two plasmids were found to be equally immunogenic at inducing antibodies to TS or inhibition of T. cruzi infection. A third plasmid, in which the TS gene was inserted into the vector VR1012, was as immunogenic as the two others. Immunization with a TS recombinant protein in alum generated a significantly higher antibody response as measured by ELISA or inhibition of TS enzymatic activity. Most relevant, this immunization reduced the mortality due to acute infection.

Trans-Sialidase Recombinant Protein Mixed with CpG Motif-Containing Oligodeoxynucleotide Induces Protective Mucosal and Systemic Trypanosoma cruzi Immunity Involving CD8+ CTL and B Cell-Mediated Cross-Priming

“…Secondary TCR encounters with homologous but nonidentical TS-encoded epitopes during progressive infection could lead to only partial TCR signaling and T cell anergy. However, previous immunizations with DNA encoding the consensus TS enzymatic sequence or recombinant TS protein have induced immunity in BALB/c mice that is protective against virulent challenges with the Y strain of T. cruzi (28,29). We have confirmed these results here, demonstrating that immunizations with DNA encoding the consensus TS enzymatic domain can protect BALB/c mice against BFT challenges with Tulahuén strain parasites, a virulent strain of T. cruzi distinct from Y strain parasites.…”

Immunotherapy ofTrypanosoma cruziInfection with DNA Vaccines in Mice

“…Because DNA vaccines have a strong Th1 bias in the immune response which they induce (39), they appear to be particularly promising for use against parasites such as T. cruzi. Indeed, immunization of mice with a DNA vaccine encoding transsialidase (8,34,37), TSA-1 (13,50), ASP-1 and ASP-2 (13), or KMP11-HSP70 fusion protein (35) leads to a Th1-type immune response that is protective in the case of TSA-1, ASP-1, ASP-2, or KMP11-HSP70. Similarly, immunization with a plasmid encoding the complement regulatory protein, but not the recombinant protein, can protect against challenge (40).…”

Enzyme-Linked Immunoassay Using Recombinant trans -Sialidase of Trypanosoma cruzi Can Be Employed for Monitoring of Patients with Chagas' Disease after Drug Treatment

“…The other is composed of 12-amino-acid repeats and is located at the C terminus (10,28). The enzyme's N-terminal domain is responsible for the induction of specific antibodies that inhibit the enzymatic activity of TS during infection (14,23,24). Moreover, the N-terminal domain has important roles in the humoral (6,15,23) and cellular (26,27) immune responses that control infection.…”

“…The enzyme's N-terminal domain is responsible for the induction of specific antibodies that inhibit the enzymatic activity of TS during infection (14,23,24). Moreover, the N-terminal domain has important roles in the humoral (6,15,23) and cellular (26,27) immune responses that control infection. Therefore, we aimed to investigate whether sera from patients with Chagas' disease specifically recognize this recombinant TS and if this recognition decreases in patients undergoing anti-T. cruzi chemotherapy with benznidazole.…”