Multi-epitope proteins for improved serological detection of Trypanosoma cruzi infection and Chagas Disease

Duthie, Malcolm S.; Guderian, Jeffery; Vallur, Aarthy C.; Misquith, Ayesha; Liang, Hong; Mohamath, Raodoh; Luquetti, Alejandro O.; Carter, Darrick; Tavares, Suelene N.B.; Reed, Steven G.

doi:10.1016/j.diagmicrobio.2015.11.006

Cited by 8 publications

(9 citation statements)

References 29 publications

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“…A search conducted at Pubmed using the keywords: "Multiepitope protein" and "diagnosis" identified 270 published articles. Out of these, only four were related to the diagnosis of CD, showing sensitivity and specificity data [40,[54][55][56]. However, none of them evaluated the potential of their antigens to detect both chagasic forms classified with the clinical form as done in this study.…”

Section: Discussionmentioning

confidence: 91%

“…Different factors may be associated with the performance of the test, such as the intrinsic characteristic of each antigen and the use of the assays in countries and regions where the genetic strains differ from those used for the development of the antigen [39][40][41]. To overcome this problem, a multiepitope-based protein could be used as an alternative to crude antigens improving sensitivity, and specificity and reducing production costs [42,43].…”

Section: Discussionmentioning

confidence: 99%

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Proof-of-Concept of a Novel Multiepitope Recombinant Protein for the Serodiagnosis of Patients with Chagas Disease

Machado¹,

Pereira²,

Maia³

et al. 2022

Preprint

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Background: Chagas disease is still a neglected disease considered a public health problem. Early diagnosis of cases is important to improve the prognosis of infected patients and prevent transmission. Serological tests are the method of choice for diagnosis. However, two serological tests are currently recommended to confirm positive cases. In this sense, more sensitive and specific serological tests need to be developed to overcome the problems currently faced. This study aimed to develop a new recombinant multiepitope protein for the diagnosis of Chagas disease, hereafter named rTC. Methods: The rTC was constructed based on amino acid sequences from different combinations of Trypanossoma cruzi antigens in the same polypeptide and tested in ELISA for detecting different Chagas disease. Results: rTC1 was able to discriminate between indeterminate (IND) and cardiac (CARD) cases and cross-reactive diseases, and healthy samples, with 96.6% sensitivity and 97.96% specificity, respectively. Conclusion: These data suggest a preliminary study that rTC1 has the po-tential to be tested in future studies against a larger serological panel for the diagnosis of Chagas disease.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Proof-of-Concept of a Novel Multiepitope Recombinant Protein for the Serodiagnosis of Patients with Chagas Disease

Machado¹,

Pereira²,

Maia³

et al. 2022

Preprint

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“…LepReact, a delayed-type hypersensitivity skin test, made from LID-1, was able to detect antigen-specific immune responses from M. leprae in guinea pigs and armadillos [72]. As to other diseases, Chagas disease detection can be improved using TcF43 and TcF26, proteins derived from the fusion of selected T. cruzi TR proteins [28]; Yin et al validated a high-accuracy ELISA assay using a recombinant protein for diagnosis of human brucellosis [27]; Ebrahimi [32].…”

Section: Discussionmentioning

confidence: 99%

“…The multi-epitope constructs enable a higher immunogenic density and diminish the cross-reaction risk of whole bacteria antigen, which is common in leprosy diagnosis [27]. Diseases such as hepatitis B [23], Chagas disease [28], cryptococcosis [25], leishmaniosis [29,30], tuberculosis [31], and toxocariasis [32] already have great results with recombinant multi-epitope proteins in their diagnosis.…”

Section: Introductionmentioning

confidence: 99%

In silico designing of a recombinant multi-epitope antigen for leprosy diagnosis

Lemes

Rodrigues

Jaiswal

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Most of the affected population lives in low-income countries and may take up to 10 years to show any clinical signs, which is how physicians diagnose it. However, due to progressive cell damage, early diagnosis is very important. The best way to confirm leprosy is through bacilloscopic, which only confirms the diagnosis and has low accuracy or PCR, that requires specialized operators and is expensive. Since the bacteria are fastidious and do not grow in any culture media, therefore, diagnosing leprosy in the lab is still a challenge. In this concern, a recombinant multi-epitope protein can be a beneficial strategy in the management of the diagnosis, as diverse immunogenic epitopes are precisely selected to detect specific antibodies. Therefore, the purposes of the present study were to select immunogenic epitopes from different relevant proteins, with immunogenic properties, and then to construct a recombinant multi-epitope protein that accuses the presence of the antibodies in the early stages of the disease, making it more than appropriate to be applied as a diagnostic tool. Results We selected 22 common proteins from both species and, using bioinformatics tools, predicted B and T cell epitopes. After multiple filtering and analyzing, we ended up with 29 epitopes {MHC-I (total 18) and MHC-II (total 11)} from 10 proteins, which were then merged into one construct. Its secondary and tertiary structures were also predicted and refined to comprise the amino acid residues in the best conformation possible. The multi-epitope protein construct was stable, non-host homologous, non-allergic, non-toxic, and elicit humoral and cellular responses. It has conformational B cell epitopes and potential to elicit IFN-γ, IL-4, and IL-10 secretion. Conclusions This novel recombinant multi-epitope protein constructed using the common epitopes from M. leprae and M. lepromatosis has a huge immunological potential, is stable, and can be lyophilized to be used in ELISA plates or even in biosensors, which are user-friendly diagnosis tools, facilitating translation into human sample tests.

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“…Synthetic peptides are less complex than proteins but can be utilized as antigens in ELISAs. Combining recombinant multiepitopic proteins results in high sensitivity and specificity (Duthie et al, 2016;Marcipar and Lagier, 2012). Nonetheless, in this study a synthetic peptide technique proved more specific than sensitive.…”

Section: Discussionmentioning

confidence: 99%

Comparative evaluation of immunoassays to improve access to diagnosis for Chagas disease in Colombia

Díaz¹,

Forsyth²,

Bernal³

et al. 2019

International Journal of Infectious Diseases

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Chagas disease affects over six million people, but less than 1% are diagnosed and treated. Complicated diagnostic processes are a major barrier. Colombia's previous diagnostic algorithm, using inhouse tests, was difficult to scale up, creating significant access barriers for patients. A new algorithm using commercially manufactured immunoassays would potentially improve access, but these tests' performance in Colombian patients with Chagas disease is not well known. Methods: We assessed seven commercially available assays. Samples (n = 501), 93.8% originating from Colombia, were characterized as positive or negative based on standard procedure at the National Reference Laboratory. Performance characteristics were calculated for individual assays and hypothetical test pairings, then compared to the existing algorithm. Results: Five of seven assays exhibited sensitivity >98% while six showed specificity >97%. A total antigen ELISA paired with a recombinant assay provided similar performance to the current diagnostic process. Six of six assays tested proved capable of detecting different Trypanosoma cruzi genetic lineages. Conclusions: The study indicated that several commercial assays accurately detect T. cruzi infection in Colombian patients. A simplified testing process with two commercial assays could perform comparably to the previous process, reducing cost and accessibility barriers and facilitating national scale-up.

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Multi-epitope proteins for improved serological detection of Trypanosoma cruzi infection and Chagas Disease

Cited by 8 publications

References 29 publications

Proof-of-Concept of a Novel Multiepitope Recombinant Protein for the Serodiagnosis of Patients with Chagas Disease

Proof-of-Concept of a Novel Multiepitope Recombinant Protein for the Serodiagnosis of Patients with Chagas Disease

In silico designing of a recombinant multi-epitope antigen for leprosy diagnosis

Comparative evaluation of immunoassays to improve access to diagnosis for Chagas disease in Colombia

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