Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

Abstract

Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-g-producing T cells.

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

“…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.…”

AU-rich Elements in the 3′-Untranslated Region of a New Mucin-type Gene Family of Trypanosoma cruzi Confers mRNA Instability and Modulates Translation Efficiency

“…In the human pathogen Trypanosoma cruzi, the ethiological agent of Chagas' disease, there are mucin-type glycoproteins that have been increasingly studied because of their role as the main sialic acid acceptors (1,2) in the reaction catalyzed by transsialidase (3,4). This unique enzymatic activity seems to have been selected during evolution to circumvent the lack of de novo synthesis of this sugar in this protozoan parasite (5).…”

“…Because of their size and structure, T. cruzi mucins are comparable to endothelial mucin-type adhesion molecules, better than to high molecular weight epithelial mucins. Additionally, T. cruzi being a digenetic parasite, there are at least two different groups of mucin molecules among life cycle stages: one present in the insect vector forms of the parasite and the other in the mammalian stage (2). T. cruzi infection is established in the mammal by the insect-derived stage metacyclic trypomastigote.…”

“…The mucin nature of the former group of TcMUC products is now clear (15). 2 The TcMUC family has about 500 members per haploid genome and many, if not all of them, are transcribed simultaneously in a given parasite population (8). The molecular masses of the products deduced from these genes, that are around 18 -20 kDa, along with the information from transfection experiments, 2 point to repeat-containing members of this family as those encoding apomucins present in the mammalian trypomastigote stage.…”

Intranasal Vaccinations with the trans -Sialidase Antigen plus CpG Adjuvant Induce Mucosal Immunity Protective against Conjunctival Trypanosoma cruzi Challenges

“…DNA vaccines encoding the catalytic domain of TS have been shown to induce immunity protective against systemic T. cruzi challenge (3,4,6,16). It has also been shown that both CD4 ϩ and CD8 ϩ T-cell epitopes are required for this TS-specific protective immunity (6).…”