TY - JOUR
T1 - A novel multi-epitope recombinant protein elicits an antigen-specific CD8+ T cells response in Trypanosoma cruzi-infected mice
AU - González-López, Cristina
AU - Chen, Wen Hsiang
AU - Alfaro-Chacón, Andrea
AU - Villanueva-Lizama, Liliana E.
AU - Rosado-Vallado, Miguel
AU - Ramirez-Sierra, Maria Jesús
AU - Teh-Poot, Christian F.
AU - Pollet, Jeroen
AU - Asojo, Oluwatoyin
AU - Jones, Kathryn M.
AU - Hotez, Peter J.
AU - Elena Bottazzi, Maria
AU - Cruz-Chan, Julio Vladimir
N1 - 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
PY - 2022/10/26
Y1 - 2022/10/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85138996418&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2022.09.068
DO - 10.1016/j.vaccine.2022.09.068
M3 - Article
C2 - 36184402
AN - SCOPUS:85138996418
SN - 0264-410X
VL - 40
SP - 6445
EP - 6449
JO - Vaccine
JF - Vaccine
IS - 45
ER -
