Evaluation of a Recombinant Trypanosoma cruzi Mucin-Like Antigen for Serodiagnosis of Chagas' Disease

Marchi, Cassiano; Noia, Javier M. Di; Frasch, Alberto C.C.; Neto, Vicente Amato; Almeida, Igor C.; Buscaglia, Carlos A.

doi:10.1128/cvi.05289-11

Cited by 48 publications

(59 citation statements)

References 35 publications

(50 reference statements)

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“…Previous studies have also proposed a chemiluminescent ELISA (CL-ELISA) with purified trypomastigote glycoproteins for the detection of lytic protective antibodies against T. cruzi in human serum (33,51,52). CL-ELISA achieved high diagnostic accuracy in both areas that are endemic (51,52) and nonendemic (33) for the disease. Detection systems, such as chemiluminescence, increase light amplification and signal duration in comparison with traditional ELISAs.…”

Section: Discussionmentioning

confidence: 99%

Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

et al. 2016

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“…The TSSA protein encoded by the CL Brener clone of T. cruzi (TSSA-CL) (13) showed Ͼ87% sensitivity in a seropositive chagasic panel from Argentina and Brazil, a value which increased to Ͼ98% when only parasitologically positive samples were considered (11). Most important, TSSA-CL showed a significant increase in specificity (97.4%) compared to that of the currently used serologic assays (11).…”

mentioning

confidence: 92%

“…The glutathione S-transferase (GST)-fusion protein bearing the repetitive domain of T. cruzi shed acute-phase antigen (SAPA) has been described (26,27). The GST fusion protein bearing the central region (from residues 24 to 61/62) of Sylvio X-10 TSSA (TSSASy ) and CL Brener TSSA (TSSA-CL 24-62 ) have also been described (11). Variants spanning partially overlapped 15mer sequences from TSSA-CL were constructed by Taq polymerase-mediated fill-in of partially complementary forward (TSSA VI Ep n Fw) and reverse (TSSA VI Ep n Rv) oligonucleotides (see Table S1 in the supplemental material) containing BamHI and EcoRI sites on their 5= ends, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Interstrain polymorphisms were shown to be focused on the central region of TSSA (12,14) and to have a major impact on its immunogenicity and antigenicity (11,12,16). Different attempts at using TSSA polymorphisms to design parasite lineage-specific serologic reagents as an indirect approach to allow for the typification of infecting T. cruzi strains have been undertaken (17,18).…”

mentioning

confidence: 99%

“…As reported, serum samples from individuals with other endemic coinfections (especially Leishmania spp.) and/or afflicted by certain autoimmune disorders cross-recognize T. cruzi antigens (6,11).…”

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confidence: 99%

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Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide-and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acidlong peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. Chagas disease is a major health and economic problem in Latin America, for which no vaccine or appropriate drugs for largescale public health interventions are yet available (1). It is caused by the protozoan Trypanosoma cruzi, found throughout the American continents in a variety of wild and domestic mammalian reservoirs, and it is transmitted by the bite of infected bloodsucking triatomine bugs. It is estimated that 8 to 10 million people are currently infected with T. cruzi and that up to 120 million individuals living in areas that are endemic for the parasite are at risk of infection (1). Increasing travel and immigration have also brought the risk of T. cruzi infection into countries that are not endemic for the parasite (2). Several efforts have successfully been undertaken to control transmission in Latin America, with a concomitant decrease in the actual numbers of acute vector-borne infections (3). However, humans can also become infected with T. cruzi through the ingestion of tainted food and fluids, receipt of contaminated blood transfusion or organ transplantation, and from mother-to-child during pregnancy/delivery (4).The diagnosis of Chagas disease is challenging because it is often asymptomatic in its acute phase and evolves into a chronic stage in which the disease course takes different clinical forms (1). In addition, and due to a major decline in parasitemia during the chronic phase, the detection of T. cruzi in blood sample...

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