Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection

Abstract Chagas disease resulting from Trypanosoma cruzi infection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. Antiparasitic treatment with benznidazole does not prevent disease progression or death in patient...

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Autores principales:	Julio V. Cruz-Chan, Liliana E. Villanueva-Lizama, Leroy Versteeg, Ashish Damania, Maria José Villar, Cristina González-López, Brian Keegan, Jeroen Pollet, Fabian Gusovsky, Peter J. Hotez, Maria Elena Bottazzi, Kathryn M. Jones
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d8ab2248bad4bc78f23356c1341a291
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spelling	oai:doaj.org-article:7d8ab2248bad4bc78f23356c1341a2912021-12-02T14:06:11ZVaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection10.1038/s41598-021-82930-w2045-2322https://doaj.org/article/7d8ab2248bad4bc78f23356c1341a2912021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82930-whttps://doaj.org/toc/2045-2322Abstract Chagas disease resulting from Trypanosoma cruzi infection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. Antiparasitic treatment with benznidazole does not prevent disease progression or death in patients with established cardiac disease. Our consortium is developing a therapeutic vaccine based on the T. cruzi flagellar—derived antigen Tc24-C4 formulated with a Toll-like receptor 4 agonist adjuvant, to complement existing chemotherapy and improve treatment efficacy. Here we demonstrate that therapeutic treatment of acutely infected mice with a reduced dose of benznidazole concurrently with vaccine treatment – also known as “vaccine-linked chemotherapy”—induced a TH17 like immune response, with significantly increased production of antigen specific IL-17A, IL-23 and IL-22, and CD8 + T lymphocytes, as well as significantly increased T. cruzi specific IFNγ-producing CD4 + T lymphocytes. Significantly reduced cardiac inflammation, fibrosis, and parasite burdens and improved survival were achieved by vaccine-linked chemotherapy and individual treatments. Importantly, low dose treatments were comparably efficacious to high dose treatments, demonstrating potential dose sparing effects. We conclude that through induction of TH17 immune responses vaccine-linked chemotherapeutic strategies could bridge the tolerability and efficacy gaps of current drug treatment in Chagasic patients.Julio V. Cruz-ChanLiliana E. Villanueva-LizamaLeroy VersteegAshish DamaniaMaria José VillarCristina González-LópezBrian KeeganJeroen PolletFabian GusovskyPeter J. HotezMaria Elena BottazziKathryn M. JonesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julio V. Cruz-Chan Liliana E. Villanueva-Lizama Leroy Versteeg Ashish Damania Maria José Villar Cristina González-López Brian Keegan Jeroen Pollet Fabian Gusovsky Peter J. Hotez Maria Elena Bottazzi Kathryn M. Jones Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
description	Abstract Chagas disease resulting from Trypanosoma cruzi infection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. Antiparasitic treatment with benznidazole does not prevent disease progression or death in patients with established cardiac disease. Our consortium is developing a therapeutic vaccine based on the T. cruzi flagellar—derived antigen Tc24-C4 formulated with a Toll-like receptor 4 agonist adjuvant, to complement existing chemotherapy and improve treatment efficacy. Here we demonstrate that therapeutic treatment of acutely infected mice with a reduced dose of benznidazole concurrently with vaccine treatment – also known as “vaccine-linked chemotherapy”—induced a TH17 like immune response, with significantly increased production of antigen specific IL-17A, IL-23 and IL-22, and CD8 + T lymphocytes, as well as significantly increased T. cruzi specific IFNγ-producing CD4 + T lymphocytes. Significantly reduced cardiac inflammation, fibrosis, and parasite burdens and improved survival were achieved by vaccine-linked chemotherapy and individual treatments. Importantly, low dose treatments were comparably efficacious to high dose treatments, demonstrating potential dose sparing effects. We conclude that through induction of TH17 immune responses vaccine-linked chemotherapeutic strategies could bridge the tolerability and efficacy gaps of current drug treatment in Chagasic patients.
format	article
author	Julio V. Cruz-Chan Liliana E. Villanueva-Lizama Leroy Versteeg Ashish Damania Maria José Villar Cristina González-López Brian Keegan Jeroen Pollet Fabian Gusovsky Peter J. Hotez Maria Elena Bottazzi Kathryn M. Jones
author_facet	Julio V. Cruz-Chan Liliana E. Villanueva-Lizama Leroy Versteeg Ashish Damania Maria José Villar Cristina González-López Brian Keegan Jeroen Pollet Fabian Gusovsky Peter J. Hotez Maria Elena Bottazzi Kathryn M. Jones
author_sort	Julio V. Cruz-Chan
title	Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
title_short	Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
title_full	Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
title_fullStr	Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
title_full_unstemmed	Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection
title_sort	vaccine-linked chemotherapy induces il-17 production and reduces cardiac pathology during acute trypanosoma cruzi infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7d8ab2248bad4bc78f23356c1341a291
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Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection

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