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

• DOI: 10.1016/j.diagmicrobio.2015.11.006
• Publication Date: 2015-11-10T20:32:40Z
• Authors: Malcolm S. Duthie; Jeffery A. Guderian; Aarthy C. Vallur; Ayesha Misquith; Hong Liang; Raodoh Mohamath; Alejandro O. Luqu...; Darrick Carter; Suelene N.B. Tavares; Steven G. Reed
• Keywords: Adult; Aged, 80 and over; Male; Trypanosoma cruzi; Protozoan Proteins; Antigens, Protozoan; Enzyme-Linked Immunosorbent Assay; Middle Aged; Sensitivity and Specificity; 3. Good health; Epitopes; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Case-Control Studies; Humans; Chagas Disease; Female; Serologic Tests; Aged

We previously reported that tandem repeat (TR) proteins from Trypanosoma cruzi could serve as targets of the antibody response and be useful as diagnostic indicators. To optimize reagents for detecting T. cruzi infection we evaluated individual TR proteins and identified several that were recognized by the majority of Chagas patient's sera collected from individuals form Brazil. We then produced novel, recombinant fusion proteins to combine the reactive TR proteins into a single diagnostic product. Direct comparison of the antibody response of serum samples that were readily detected by the established fusion antigen used in commercial detection of Chagas disease, TcF, revealed strong responses to TcF43 and TcF26 proteins. While the TcF43 and TcF26 antigens enhanced detection and strength of signal, they did not compromise the specificity of detection compared to that obtained with TcF. Finally, it was apparent by testing against a panel of 84 serum samples assembled on the basis of moderate or weak reactivity against TcF (mostly signal:noise <5) that TcF43 and TcF26 could more strongly detected by many of the sera that had low TcF antibody levels. Taken together, these data indicate that TcF43 and TcF26 could be used to enhance the detection of T. cruzi infection as well as supporting a diagnosis of Chagas disease.