The high identity of the Trypanosoma cruzi Group‐I of trans‐sialidases points them as promising vaccine immunogens

PACINI, MARIA FLORENCIA; PERDOMINI, ADRIÁN; BULFONI BALBI, CAMILA; DINATALE, BRENDA; HERRERA, FERNANDO E.; PEREZ, ANA ROSA; MARCIPAR, IVÁN

PROTEINS: STRUCTURE, FUNCTION AND GENETICS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2023

0887-3585

Trans-sialidase (TS) superfamily of proteins comprises eight subgroups, being the proteins of Group-I (TS-GI) promising immunogens in vaccine approaches against Trypanosoma cruzi. Strikingly, TS-GI antigenic variability among parasite lineages and theirinfluence on vaccine development has not been previously analyzed. Here, a searchin GenBank detects 49 TS-GI indexed sequences, whereas the main infecting humandifferent parasite discrete typing units (DTU) are represented. In silico comparisonamong these sequences indicate that they share an identity above 92%. Moreover,the antigenic regions (T-cell and B-cell epitopes) are conserved in most sequences orpresent amino acid substitutions that scarcely may alter the antigenicity. Additionally,since the generic term TS is usually used to refer to different immunogens of thisbroad family, a further in silico analysis of the TS-GI-derived fragments tested in preclinical vaccines was done to determine the coverage and identity among them,showing that overall amino acid identity of vaccine immunogens is high, but the segment coverage varies widely. Accordingly, strong H-2K, H-2I, and B-cell epitopes aredissimilarly represented among vaccine TS-derived fragments depending on theextension of the TG-GI sequence used. Moreover, bioinformatic analysis detected aset of 150 T-cell strong epitopes among the DTU-indexed sequences that stronglybind human HLA-I supertypes. In all currently reported experimental vaccines basedon TS-GI fragments, mapping these 150 epitopes showed that they are moderatelyrepresented. However, despite vaccine epitopes do not present all the substitutionsobserved in the DTUs, these regions of the proteins are equally recognized by thesame HLAs. Interestingly, the predictions regarding global and South American population coverage estimated in these 150 epitopes are similar to the estimations inexperimental vaccines when the complete sequence of TS-GI is used as an antigen.In silico prediction also shows that a number of these MHC-I restricted T-cell strongepitopes could be also cross-recognized by HLA-I supertypes and H-2Kb or H-2Kdbackgrounds, indicating that these mice may be used to improve and facilitate thedevelopment of new TS-based vaccines and suggesting an immunogenic and protective potential in humans. Further molecular docking analyses were performed tostrengthen these results. Taken together, different strategies that would cover more