Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep

[EN]Vaccination is the most effective tool for paratuberculosis control. Currently, available vaccines prevent the progression of clinical disease in most animals but do not fully protect them against infection and induce the formation of an injection site granuloma. The precise mechanisms that oper...

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Autores: Criado Boyero, Miguel, Reyes Ávila, Luis Ernesto, García Marín, Juan Francisco, Gutiérrez Expósito, Daniel, Zapico Sánchez, David, Espinosa Cerrato, José, Pérez Pérez, Valentín
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/25803
Acceso en línea:https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1284902/full
https://hdl.handle.net/10612/25803
Access Level:acceso abierto
Palabra clave:Inmunología
Sanidad animal
Veterinaria
Adjuvants
Paratuberculosis
Vaccine injection-site
Granuloma
Gudair
Silirum
2412.10 Vacunas
3109.03 Inmunología
3104.07 Ovinos
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spelling Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheepCriado Boyero, MiguelReyes Ávila, Luis ErnestoGarcía Marín, Juan FranciscoGutiérrez Expósito, DanielZapico Sánchez, DavidEspinosa Cerrato, JoséPérez Pérez, ValentínInmunologíaSanidad animalVeterinariaAdjuvantsParatuberculosisVaccine injection-siteGranulomaGudairSilirum2412.10 Vacunas3109.03 Inmunología3104.07 Ovinos[EN]Vaccination is the most effective tool for paratuberculosis control. Currently, available vaccines prevent the progression of clinical disease in most animals but do not fully protect them against infection and induce the formation of an injection site granuloma. The precise mechanisms that operate in response to vaccination and granuloma development, as well as the effect that adjuvants could trigger, have not been fully investigated. Therefore, this study aimed to investigate the injection site granulomas induced by two inactivated paratuberculosis vaccines, which differ in the adjuvant employed. Two groups of 45-day-old lambs were immunized with two commercially available vaccines—one (n = 4) with Gudair® and the other (n = 4) with Silirum®. A third group (n = 4) was not vaccinated and served as control. The peripheral humoral response was assessed throughout the study by a commercial anti-Mycobacterium avium subspecies paratuberculosis (Map) antibody indirect ELISA, and the cellular immune response was assessed similarly by the IFN-γ release and comparative intradermal tests. The injection site granulomas were measured during the experiment and sampled at 75 days post-vaccination (dpv) when the animals were euthanized. The tissue damage, antigen and adjuvant distribution, and the presence and amount of immune cells were then determined and assessed by immunohistochemical methods. Antibodies against Map antigens; a general macrophage marker (Iba1), M1 (iNOS), and M2 (CD204) macrophages; T (CD3), B (CD20), and γδ T lymphocytes, proteins MHC-II and NRAMP1, and cytokines IL-4, IL-10, TNF, and IFN-γ were employed. Silirum® elicited a stronger peripheral cellular immune response than Gudair®, while the latter induced larger granulomas and more tissue damage at the site of injection. Additionally, adjuvant and Map antigen distribution throughout the granulomatous inflammatory infiltrate, as well as the NRAMP1 cell expression, which is linked to antigen phagocytosis, were highly irregular. In Silirum® induced granulomas, a higher number of MHC-II and TNF-expressing cells and a lower number of M2 macrophages suggested an improved antigen presentation, which could be due to the better antigen distribution and reduced tissue damage induced by this vaccine.SIThe author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the national project RTI2018–099496-B-I00 and PID2021–125807OB-C21, from the “Agencia Estatal de Investigación”, of the Spanish Ministry of Science and Innovation. MC acknowledges the receipt of a pre-doctoral grant (PRE2019–087309) from MCIN/AEI/ 10.13039/501100011033 and FSE “El FSE invierte en tu futuro” and DZ of a predoctoral contract of the University of León. Zendal (Porriño, Spain), supplied Gudair ® and Silirum ® vaccines.Frontiers MediaSanidad AnimalFacultad de Veterinaria2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1284902/fullhttps://hdl.handle.net/10612/25803reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad de LeónInglésinfo:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/RTI2018–099496-B-I00info:eu-repo/grantAgreement/AEI/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PID2021–125807OB-C21http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/258032026-06-24T12:43:27Z
dc.title.none.fl_str_mv Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
title Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
spellingShingle Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
Criado Boyero, Miguel
Inmunología
Sanidad animal
Veterinaria
Adjuvants
Paratuberculosis
Vaccine injection-site
Granuloma
Gudair
Silirum
2412.10 Vacunas
3109.03 Inmunología
3104.07 Ovinos
title_short Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
title_full Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
title_fullStr Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
title_full_unstemmed Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
title_sort Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep
dc.creator.none.fl_str_mv Criado Boyero, Miguel
Reyes Ávila, Luis Ernesto
García Marín, Juan Francisco
Gutiérrez Expósito, Daniel
Zapico Sánchez, David
Espinosa Cerrato, José
Pérez Pérez, Valentín
author Criado Boyero, Miguel
author_facet Criado Boyero, Miguel
Reyes Ávila, Luis Ernesto
García Marín, Juan Francisco
Gutiérrez Expósito, Daniel
Zapico Sánchez, David
Espinosa Cerrato, José
Pérez Pérez, Valentín
author_role author
author2 Reyes Ávila, Luis Ernesto
García Marín, Juan Francisco
Gutiérrez Expósito, Daniel
Zapico Sánchez, David
Espinosa Cerrato, José
Pérez Pérez, Valentín
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sanidad Animal
Facultad de Veterinaria
dc.subject.none.fl_str_mv Inmunología
Sanidad animal
Veterinaria
Adjuvants
Paratuberculosis
Vaccine injection-site
Granuloma
Gudair
Silirum
2412.10 Vacunas
3109.03 Inmunología
3104.07 Ovinos
topic Inmunología
Sanidad animal
Veterinaria
Adjuvants
Paratuberculosis
Vaccine injection-site
Granuloma
Gudair
Silirum
2412.10 Vacunas
3109.03 Inmunología
3104.07 Ovinos
description [EN]Vaccination is the most effective tool for paratuberculosis control. Currently, available vaccines prevent the progression of clinical disease in most animals but do not fully protect them against infection and induce the formation of an injection site granuloma. The precise mechanisms that operate in response to vaccination and granuloma development, as well as the effect that adjuvants could trigger, have not been fully investigated. Therefore, this study aimed to investigate the injection site granulomas induced by two inactivated paratuberculosis vaccines, which differ in the adjuvant employed. Two groups of 45-day-old lambs were immunized with two commercially available vaccines—one (n = 4) with Gudair® and the other (n = 4) with Silirum®. A third group (n = 4) was not vaccinated and served as control. The peripheral humoral response was assessed throughout the study by a commercial anti-Mycobacterium avium subspecies paratuberculosis (Map) antibody indirect ELISA, and the cellular immune response was assessed similarly by the IFN-γ release and comparative intradermal tests. The injection site granulomas were measured during the experiment and sampled at 75 days post-vaccination (dpv) when the animals were euthanized. The tissue damage, antigen and adjuvant distribution, and the presence and amount of immune cells were then determined and assessed by immunohistochemical methods. Antibodies against Map antigens; a general macrophage marker (Iba1), M1 (iNOS), and M2 (CD204) macrophages; T (CD3), B (CD20), and γδ T lymphocytes, proteins MHC-II and NRAMP1, and cytokines IL-4, IL-10, TNF, and IFN-γ were employed. Silirum® elicited a stronger peripheral cellular immune response than Gudair®, while the latter induced larger granulomas and more tissue damage at the site of injection. Additionally, adjuvant and Map antigen distribution throughout the granulomatous inflammatory infiltrate, as well as the NRAMP1 cell expression, which is linked to antigen phagocytosis, were highly irregular. In Silirum® induced granulomas, a higher number of MHC-II and TNF-expressing cells and a lower number of M2 macrophages suggested an improved antigen presentation, which could be due to the better antigen distribution and reduced tissue damage induced by this vaccine.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1284902/full
https://hdl.handle.net/10612/25803
url https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1284902/full
https://hdl.handle.net/10612/25803
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/RTI2018–099496-B-I00
info:eu-repo/grantAgreement/AEI/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PID2021–125807OB-C21
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Universidad de León
instname_str Universidad de León
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
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repository.mail.fl_str_mv
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