Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Autores
Bontempi, Iván; Vicco, Miguel Hernán; Cabrera, Gabriel Gustavo; Villar, Silvina Raquel; González, Florencia Belén; Roggero, Eduardo Angel; Ameloot, Paul; Callewaert, Nico; Perez, Ana Rosa; Marcipar, Ivan Sergio
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen–adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of vaccines designed to control other intracellular infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific IgG response with titers >106 and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and IL-10 by splenocytes and a strong IFN-γ secretion by CD8+ T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute infection, when the parasitemia is highest in this infection model (day 21), mTS-IMX immunized mice had ∼50 times less parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against Chagas disease can be achieved by a protein antigen–adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi vaccine candidate to be tested in clinical trials.
Fil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vicco, Miguel Hernán. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabrera, Gabriel Gustavo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: Roggero, Eduardo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: Ameloot, Paul. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; Bélgica
Fil: Callewaert, Nico. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; Bélgica
Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: Marcipar, Ivan Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Trypanosoma Cruzi
Iscom
Trans-Sialidase
Vaccine
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/13440
Acceder
id CONICETDig_3ec61e684cfbbfaac15bb05e6b94e812
oai_identifier_str oai:ri.conicet.gov.ar:11336/13440
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas diseaseBontempi, IvánVicco, Miguel HernánCabrera, Gabriel GustavoVillar, Silvina RaquelGonzález, Florencia BelénRoggero, Eduardo AngelAmeloot, PaulCallewaert, NicoPerez, Ana RosaMarcipar, Ivan SergioTrypanosoma CruziIscomTrans-SialidaseVaccinehttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen–adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of vaccines designed to control other intracellular infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific IgG response with titers >106 and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and IL-10 by splenocytes and a strong IFN-γ secretion by CD8+ T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute infection, when the parasitemia is highest in this infection model (day 21), mTS-IMX immunized mice had ∼50 times less parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against Chagas disease can be achieved by a protein antigen–adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi vaccine candidate to be tested in clinical trials.Fil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vicco, Miguel Hernán. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabrera, Gabriel Gustavo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; ArgentinaFil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; ArgentinaFil: Roggero, Eduardo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; ArgentinaFil: Ameloot, Paul. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; BélgicaFil: Callewaert, Nico. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; BélgicaFil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; ArgentinaFil: Marcipar, Ivan Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2015-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13440Bontempi, Iván; Vicco, Miguel Hernán; Cabrera, Gabriel Gustavo; Villar, Silvina Raquel; González, Florencia Belén; et al.; Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease; Elsevier; Vaccine; 33; 10; 3-2015; 1274-12830264-410Xenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.vaccine.2015.01.044info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0264410X15000882info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:41Zoai:ri.conicet.gov.ar:11336/13440instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:49:42.082CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
title Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
spellingShingle Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
Bontempi, Iván
Trypanosoma Cruzi
Iscom
Trans-Sialidase
Vaccine
title_short Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
title_full Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
title_fullStr Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
title_full_unstemmed Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
title_sort Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease
dc.creator.none.fl_str_mv Bontempi, Iván
Vicco, Miguel Hernán
Cabrera, Gabriel Gustavo
Villar, Silvina Raquel
González, Florencia Belén
Roggero, Eduardo Angel
Ameloot, Paul
Callewaert, Nico
Perez, Ana Rosa
Marcipar, Ivan Sergio
author Bontempi, Iván
author_facet Bontempi, Iván
Vicco, Miguel Hernán
Cabrera, Gabriel Gustavo
Villar, Silvina Raquel
González, Florencia Belén
Roggero, Eduardo Angel
Ameloot, Paul
Callewaert, Nico
Perez, Ana Rosa
Marcipar, Ivan Sergio
author_role author
author2 Vicco, Miguel Hernán
Cabrera, Gabriel Gustavo
Villar, Silvina Raquel
González, Florencia Belén
Roggero, Eduardo Angel
Ameloot, Paul
Callewaert, Nico
Perez, Ana Rosa
Marcipar, Ivan Sergio
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trypanosoma Cruzi
Iscom
Trans-Sialidase
Vaccine
topic Trypanosoma Cruzi
Iscom
Trans-Sialidase
Vaccine
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen–adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of vaccines designed to control other intracellular infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific IgG response with titers >106 and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and IL-10 by splenocytes and a strong IFN-γ secretion by CD8+ T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute infection, when the parasitemia is highest in this infection model (day 21), mTS-IMX immunized mice had ∼50 times less parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against Chagas disease can be achieved by a protein antigen–adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi vaccine candidate to be tested in clinical trials.
Fil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vicco, Miguel Hernán. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabrera, Gabriel Gustavo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: Roggero, Eduardo Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: Ameloot, Paul. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; Bélgica
Fil: Callewaert, Nico. Vlaams Instituut voor Biotechnologie; Bélgica. University of Ghent; Bélgica
Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Cs.medicas; Argentina
Fil: Marcipar, Ivan Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen–adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of vaccines designed to control other intracellular infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific IgG response with titers >106 and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and IL-10 by splenocytes and a strong IFN-γ secretion by CD8+ T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute infection, when the parasitemia is highest in this infection model (day 21), mTS-IMX immunized mice had ∼50 times less parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against Chagas disease can be achieved by a protein antigen–adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi vaccine candidate to be tested in clinical trials.
publishDate 2015
dc.date.none.fl_str_mv 2015-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/13440
Bontempi, Iván; Vicco, Miguel Hernán; Cabrera, Gabriel Gustavo; Villar, Silvina Raquel; González, Florencia Belén; et al.; Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease; Elsevier; Vaccine; 33; 10; 3-2015; 1274-1283
0264-410X
url http://hdl.handle.net/11336/13440
identifier_str_mv Bontempi, Iván; Vicco, Miguel Hernán; Cabrera, Gabriel Gustavo; Villar, Silvina Raquel; González, Florencia Belén; et al.; Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease; Elsevier; Vaccine; 33; 10; 3-2015; 1274-1283
0264-410X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.vaccine.2015.01.044
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0264410X15000882
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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