Abstract
Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.
Highlights
Chagas disease is a chronic disease caused by the protozoan parasite Trypanosoma cruzi, transmitted by hematophagous triatomine bugs through the direct contact of their infected feces with the skin, following a blood meal
In this study we assessed the response of mononuclear cells from Mexican Chagasic patients to the stimulation by both antigens
We found that both proteins are able to recall a secondary immune response, induced during natural infection in some patients, which is characterized by memory cells that can proliferate, differentiate and produce cytokines
Summary
Chagas disease is a chronic disease caused by the protozoan parasite Trypanosoma cruzi, transmitted by hematophagous triatomine bugs through the direct contact of their infected feces with the skin, following a blood meal. Other transmission routes include blood transfusion, organ transplantation, congenital and oral transmission (through ingestion of food or water contaminated with infected feces) [1]. At least 5.7 million people are infected and 70.2 million are at risk of infection worldwide [2], with the majority in Latin America, but new cases of autochthonous transmission have been reported in the southern USA [3]. In Mexico, the estimated prevalence is at least 0.65%, with 1.1 million people infected with T. cruzi. New cases of Chagas disease are underreported and the prevalence is likely much higher [6,7]
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