# In Silico Design and Evaluation of TcGAPDH as a Vaccine Against Chagas Disease: A Reverse Vaccinology Approach

**Authors:** Veronica Nava-Cuamatzi, Ricardo Enrique Buendia-Corona, María Cristina González-Vázquez, Maria Lilia Cedillo-Ramirez, Alejandro Carabarin-Lima

PMC · DOI: 10.1007/s11686-026-01221-4 · 2026-02-16

## TL;DR

This study explores TcGAPDH as a potential vaccine candidate for Chagas disease using computational methods to assess its immunogenic properties.

## Contribution

The novel contribution is the in silico evaluation of TcGAPDH as a vaccine candidate using reverse vaccinology techniques.

## Key findings

- TcGAPDH was found to induce a Th1-type immune response characterized by IFN-γ and IL-2.
- Molecular docking and dynamics simulations showed favorable interactions between TcGAPDH and TLR2/TLR4 receptors.
- The predicted immune response and stable interactions suggest TcGAPDH's potential as a vaccine candidate.

## Abstract

Purpose

The current treatment for Chagas disease, caused by Trypanosoma cruzi, presents significant limitations due to its variable efficacy depending on the stage of the disease and its associated adverse effects. This issue has driven research and the development of new therapeutic and preventive strategies, with a particular emphasis on vaccine design.

Materials and methods

In the present study, a bioinformatics approach was employed to evaluate T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) as a potential vaccine candidate by analysing its physicochemical and immunogenic properties.

Results

In this analysis, epitopes for B and T lymphocytes were predicted, and a predictive immune response determined that TcGAPDH has the capacity to induce a Th1-type response driven by IFN-γ and IL-2. Finally, molecular docking and dynamics simulation demonstrated favourable interaction between TcGAPDH and TLR2/TLR4 receptors, which remained constant throughout a 300 ns simulation.

Conclusions

These findings highlight the immunogenic potential of TcGAPDH and support its feasibility as a promising candidate for the development of a vaccine against Chagas disease.

The online version contains supplementary material available at 10.1007/s11686-026-01221-4.

## Linked entities

- **Proteins:** TLR2 (toll like receptor 2), TLR4 (toll like receptor 4)
- **Diseases:** Chagas disease (MONDO:0001444)
- **Species:** Trypanosoma cruzi (taxon 5693)

## Full-text entities

- **Genes:** HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}
- **Diseases:** megaesophagus and megacolon (MESH:D004931), renal and hepatic dysfunction (MESH:D008107), conditions (MESH:D020763), meningoencephalitis (MESH:D008590), DTU-I (MESH:D006969), myocarditis (MESH:D009205), NTDs (MESH:D058069), Chronic Chagasic Cardiomyopathy (MESH:D009202), infected (MESH:D007239), toxicity (MESH:D064420), cardiopathies (MESH:C536187), DTU III (MESH:C537189), deaths (MESH:D003643), CD (MESH:D014355), proinflammatory cytokines (MESH:D000080424), parasitic infection (MESH:D010272), cardiac (MESH:D006331), allergic reactions (MESH:D004342)
- **Chemicals:** N (MESH:D009584), G3P (MESH:D005986), T (MESH:D014316), Salt (MESH:D012492), 1,3-bisphosphoglycerate (MESH:C015891), inorganic phosphate (MESH:D010710), glutamic acid (MESH:D018698), nifurtimox (MESH:D009547), asparagine (MESH:D001216), E (MESH:D004540), water (MESH:D014867), reactive nitrogen species (MESH:D026361), amino acid (MESH:D000596), Cl- (MESH:D002713), AllerTOP (-), Na + (MESH:D012964), hydrogen (MESH:D006859), NAD + (MESH:D009243), threonine (MESH:D013912), ROS (MESH:D017382), GPI (MESH:D017261), benznidazole (MESH:C009999)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Escherichia coli (E. coli, species) [taxon 562], Trypanosoma cruzi (species) [taxon 5693], Streptococcus pyogenes (species) [taxon 1314], Schistosoma mansoni (species) [taxon 6183], Eimeria (genus) [taxon 5800], Homo sapiens (human, species) [taxon 9606], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Trypanosoma brucei (species) [taxon 5691], Leishmania (subgenus) [taxon 38568], Listeria monocytogenes (species) [taxon 1639]
- **Mutations:** T62E, N62E, T399I, K358R, D299G

## Figures

17 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909448/full.md

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Source: https://tomesphere.com/paper/PMC12909448