A novel multi-epitope recombinant protein elicits an antigen-specific CD8+ T cells response in Trypanosoma cruzi-infected mice

Cristina González-López, Wen Hsiang Chen, Andrea Alfaro-Chacón, Liliana E. Villanueva-Lizama, Miguel Rosado-Vallado, Maria Jesús Ramirez-Sierra, Christian F. Teh-Poot, Jeroen Pollet, Oluwatoyin Asojo, Kathryn M. Jones, Peter J. Hotez, Maria Elena Bottazzi, Julio Vladimir Cruz-Chan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

About 6.5 million people worldwide are afflicted by Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi. The development of a therapeutic vaccine to prevent the progression of Chagasic cardiomyopathy has been proposed as an alternative for antiparasitic chemotherapy. Bioinformatics tools can predict MHC class I CD8 + epitopes for inclusion in a single recombinant protein with the goal to develop a multivalent vaccine. We expressed a novel recombinant protein Tc24-C4.10E harboring ten nonameric CD8 + epitopes and using Tc24-C4 protein as scaffold to evaluate the therapeutic effect in acute T. cruzi infection. T. cruzi-infected mice were immunized with Tc24-C4.10E or Tc24-C4 in a 50-day model of acute infection. Tc24-C4.10E-treated mice showed a decreased parasitemia compared to the Tc24-C4 (non-adjuvant) immunized mice or control group. Moreover, Tc24-C4.10E induced a higher stimulation index of CD8 + T cells producing IFNγ and IL-4 cytokines. These results suggest that the addition of the MHC Class I epitopes to Tc24-C4 can synergize the antigen-specific cellular immune responses, providing proof-of-concept that this approach could lead to the development of a promising vaccine candidate for Chagas disease.

Original languageEnglish
Pages (from-to)6445-6449
Number of pages5
JournalVaccine
Volume40
Issue number45
DOIs
Publication statusPublished - 26 Oct 2022

Bibliographical note

Funding Information:
This work was funded by the Robert J. Kleberg Jr. and Helen C. KlebergFoundation, CONACyT – PCC (319746), and the Carlos Slim Foundation.

Publisher Copyright: © 2022 The Authors

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