Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response

Autores
Pschunder, Bernarda; Locati, Lucía; López, Oriana; Martin Aispuro, Pablo; Zurita, Maria Eugenia; Stuible, Matthew; Durocher, Yves; Hozbor, Daniela Flavia
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMV Bp ) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMV Bp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMV Bp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMV Bp and the immunogens at varying levels. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMV Bp , specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001).When assessing the adjuvant properties of OMV Bp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMV E.coli ) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species.Nonetheless, it's crucial to highlight that OMV Bp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMV Bp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.
Fil: Pschunder, Bernarda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Locati, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: López, Oriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Martin Aispuro, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Zurita, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Stuible, Matthew. Human Health Therapeutics Research Centre; Canadá
Fil: Durocher, Yves. Human Health Therapeutics Research Centre; Canadá
Fil: Hozbor, Daniela Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Materia
BORDETELLA PERTUSSIS
OUTER-MEMBRANE VESICLES
ADJUVANT
ANTIBODIES
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:11336/265215
Acceder
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spelling Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased responsePschunder, BernardaLocati, LucíaLópez, OrianaMartin Aispuro, PabloZurita, Maria EugeniaStuible, MatthewDurocher, YvesHozbor, Daniela FlaviaBORDETELLA PERTUSSISOUTER-MEMBRANE VESICLESADJUVANTANTIBODIEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMV Bp ) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMV Bp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMV Bp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMV Bp and the immunogens at varying levels. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMV Bp , specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001).When assessing the adjuvant properties of OMV Bp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMV E.coli ) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species.Nonetheless, it's crucial to highlight that OMV Bp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMV Bp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.Fil: Pschunder, Bernarda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Locati, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: López, Oriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Martin Aispuro, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Zurita, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Stuible, Matthew. Human Health Therapeutics Research Centre; CanadáFil: Durocher, Yves. Human Health Therapeutics Research Centre; CanadáFil: Hozbor, Daniela Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFrontiers Media2024-03info: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/11336/265215Pschunder, Bernarda; Locati, Lucía; López, Oriana; Martin Aispuro, Pablo; Zurita, Maria Eugenia; et al.; Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response; Frontiers Media; Frontiers in Immunology; 15; 3-2024; 1-121664-32241664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2024.1387534info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:10Zoai:ri.conicet.gov.ar:11336/265215instacron: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 10:06:10.758CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
title Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
spellingShingle Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
Pschunder, Bernarda
BORDETELLA PERTUSSIS
OUTER-MEMBRANE VESICLES
ADJUVANT
ANTIBODIES
title_short Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
title_full Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
title_fullStr Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
title_full_unstemmed Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
title_sort Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
dc.creator.none.fl_str_mv Pschunder, Bernarda
Locati, Lucía
López, Oriana
Martin Aispuro, Pablo
Zurita, Maria Eugenia
Stuible, Matthew
Durocher, Yves
Hozbor, Daniela Flavia
author Pschunder, Bernarda
author_facet Pschunder, Bernarda
Locati, Lucía
López, Oriana
Martin Aispuro, Pablo
Zurita, Maria Eugenia
Stuible, Matthew
Durocher, Yves
Hozbor, Daniela Flavia
author_role author
author2 Locati, Lucía
López, Oriana
Martin Aispuro, Pablo
Zurita, Maria Eugenia
Stuible, Matthew
Durocher, Yves
Hozbor, Daniela Flavia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BORDETELLA PERTUSSIS
OUTER-MEMBRANE VESICLES
ADJUVANT
ANTIBODIES
topic BORDETELLA PERTUSSIS
OUTER-MEMBRANE VESICLES
ADJUVANT
ANTIBODIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMV Bp ) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMV Bp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMV Bp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMV Bp and the immunogens at varying levels. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMV Bp , specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001).When assessing the adjuvant properties of OMV Bp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMV E.coli ) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species.Nonetheless, it's crucial to highlight that OMV Bp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMV Bp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.
Fil: Pschunder, Bernarda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Locati, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: López, Oriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Martin Aispuro, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Zurita, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Stuible, Matthew. Human Health Therapeutics Research Centre; Canadá
Fil: Durocher, Yves. Human Health Therapeutics Research Centre; Canadá
Fil: Hozbor, Daniela Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
description For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMV Bp ) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMV Bp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMV Bp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMV Bp and the immunogens at varying levels. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMV Bp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMV Bp , specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001).When assessing the adjuvant properties of OMV Bp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMV E.coli ) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species.Nonetheless, it's crucial to highlight that OMV Bp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMV Bp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.
publishDate 2024
dc.date.none.fl_str_mv 2024-03
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/11336/265215
Pschunder, Bernarda; Locati, Lucía; López, Oriana; Martin Aispuro, Pablo; Zurita, Maria Eugenia; et al.; Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response; Frontiers Media; Frontiers in Immunology; 15; 3-2024; 1-12
1664-3224
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265215
identifier_str_mv Pschunder, Bernarda; Locati, Lucía; López, Oriana; Martin Aispuro, Pablo; Zurita, Maria Eugenia; et al.; Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response; Frontiers Media; Frontiers in Immunology; 15; 3-2024; 1-12
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2024.1387534
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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