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

doi:10.1016/j.vaccine.2022.09.068

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

Virology

Research output: Contribution to journal › Article › Academic › peer-review

9 Citations (Scopus)

81 Downloads (Pure)

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 language	English
Pages (from-to)	6445-6449
Number of pages	5
Journal	Vaccine
Volume	40
Issue number	45
DOIs	https://doi.org/10.1016/j.vaccine.2022.09.068
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1016/j.vaccine.2022.09.068Licence: CC BY

1-s2.0-S0264410X22011884-mainFinal published version, 952 KBLicence: CC BY

Cite this

González-López, C., Chen, W. H., Alfaro-Chacón, A., Villanueva-Lizama, L. E., Rosado-Vallado, M., Ramirez-Sierra, M. J., Teh-Poot, C. F., Pollet, J., Asojo, O., Jones, K. M., Hotez, P. J., Elena Bottazzi, M., & Cruz-Chan, J. V. (2022). A novel multi-epitope recombinant protein elicits an antigen-specific CD8+ T cells response in Trypanosoma cruzi-infected mice. Vaccine, 40(45), 6445-6449. https://doi.org/10.1016/j.vaccine.2022.09.068

@article{074466164e7d4c2684c622d07d88d2b0,

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

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.",

author = "Cristina Gonz{\'a}lez-L{\'o}pez and Chen, \{Wen Hsiang\} and Andrea Alfaro-Chac{\'o}n and Villanueva-Lizama, \{Liliana E.\} and Miguel Rosado-Vallado and Ramirez-Sierra, \{Maria Jes{\'u}s\} and Teh-Poot, \{Christian F.\} and Jeroen Pollet and Oluwatoyin Asojo and Jones, \{Kathryn M.\} and Hotez, \{Peter J.\} and \{Elena Bottazzi\}, Maria and Cruz-Chan, \{Julio Vladimir\}",

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: {\textcopyright} 2022 The Authors",

year = "2022",

month = oct,

day = "26",

doi = "10.1016/j.vaccine.2022.09.068",

language = "English",

volume = "40",

pages = "6445--6449",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier Ltd.",

number = "45",

}

González-López, C, Chen, WH, Alfaro-Chacón, A, Villanueva-Lizama, LE, Rosado-Vallado, M, Ramirez-Sierra, MJ, Teh-Poot, CF, Pollet, J, Asojo, O, Jones, KM, Hotez, PJ, Elena Bottazzi, M & Cruz-Chan, JV 2022, 'A novel multi-epitope recombinant protein elicits an antigen-specific CD8+ T cells response in Trypanosoma cruzi-infected mice', Vaccine, vol. 40, no. 45, pp. 6445-6449. https://doi.org/10.1016/j.vaccine.2022.09.068

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 - https://www.scopus.com/pages/publications/85138996418

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 -

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

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this