Cargando…

Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease, a chronic debilitating condition affecting ruminants causing significant economic losses to the dairy industry. Available inactivated vaccines are not effective in controlling the di...

Descripción completa

Detalles Bibliográficos
Autores principales: Hanafy, Mostafa, Hansen, Chungyi, Phanse, Yashdeep, Wu, Chia-wei, Nelson, Kathryn, Aschenbroich, Sophie A., Talaat, Adel M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868903/
https://www.ncbi.nlm.nih.gov/pubmed/36699320
http://dx.doi.org/10.3389/fvets.2022.1046704
_version_ 1784876648755101696
author Hanafy, Mostafa
Hansen, Chungyi
Phanse, Yashdeep
Wu, Chia-wei
Nelson, Kathryn
Aschenbroich, Sophie A.
Talaat, Adel M.
author_facet Hanafy, Mostafa
Hansen, Chungyi
Phanse, Yashdeep
Wu, Chia-wei
Nelson, Kathryn
Aschenbroich, Sophie A.
Talaat, Adel M.
author_sort Hanafy, Mostafa
collection PubMed
description Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease, a chronic debilitating condition affecting ruminants causing significant economic losses to the dairy industry. Available inactivated vaccines are not effective in controlling the disease and vaccinated animals can continue to infect newly born calves. Recently, we have shown that a live-attenuated vaccine candidate (pgsN) is protective in goats and calves following challenge with virulent strains of M. paratuberculosis. To decipher the dynamics of the immune responses elicited by both live-attenuated and inactivated vaccines, we analyzed key immunological parameters of goats immunized through different routes when a marker-less pgsN vaccine was used. Within a few weeks, the inactivated vaccine triggered the formation of granulomas both at the site of inoculation and in regional lymph nodes, that increased in size over time and persisted until the end of the experiment. In contrast, granulomas induced by the pgsN vaccine were small and subsided during the study. Interestingly, in this vaccine group, histology demonstrated an initial abundance of intra-histiocytic mycobacterial bacilli at the site of inoculation, with recruitment of very minimal T lymphocytes to poorly organized granulomas. Over time, granulomas became more organized, with recruitment of greater numbers of T and B lymphocytes, which coincided with a lack of mycobacteria. For the inactivated vaccine group, mycobacterial bacilli were identified extracellularly within the center of caseating granulomas, with relatively equal proportions of B- and T-lymphocytes maintained across both early and late times. Despite the differences in granuloma-specific lymphocyte recruitment, markers for cell-mediated immunity (e.g., IFN-γ release) were robust in both injected pgsN and inactivated vaccine groups. In contrast, the intranasal live-attenuated vaccine did not elicit any reaction at site of inoculation, nor cell-mediated immune responses. Finally, 80% of animals in the inactivated vaccine group significantly reacted to purified protein derivatives from M. bovis, while reactivity was detected in only 20% of animals receiving pgsN vaccine, suggesting a higher level of cross reactivity for bovine tuberculosis when inactivated vaccine is used. Overall, these results depict the cellular recruitment strategies driving immune responses elicited by both live-attenuated and inactivated vaccines that target Johne's disease.
format Online
Article
Text
id pubmed-9868903
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-98689032023-01-24 Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats Hanafy, Mostafa Hansen, Chungyi Phanse, Yashdeep Wu, Chia-wei Nelson, Kathryn Aschenbroich, Sophie A. Talaat, Adel M. Front Vet Sci Veterinary Science Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease, a chronic debilitating condition affecting ruminants causing significant economic losses to the dairy industry. Available inactivated vaccines are not effective in controlling the disease and vaccinated animals can continue to infect newly born calves. Recently, we have shown that a live-attenuated vaccine candidate (pgsN) is protective in goats and calves following challenge with virulent strains of M. paratuberculosis. To decipher the dynamics of the immune responses elicited by both live-attenuated and inactivated vaccines, we analyzed key immunological parameters of goats immunized through different routes when a marker-less pgsN vaccine was used. Within a few weeks, the inactivated vaccine triggered the formation of granulomas both at the site of inoculation and in regional lymph nodes, that increased in size over time and persisted until the end of the experiment. In contrast, granulomas induced by the pgsN vaccine were small and subsided during the study. Interestingly, in this vaccine group, histology demonstrated an initial abundance of intra-histiocytic mycobacterial bacilli at the site of inoculation, with recruitment of very minimal T lymphocytes to poorly organized granulomas. Over time, granulomas became more organized, with recruitment of greater numbers of T and B lymphocytes, which coincided with a lack of mycobacteria. For the inactivated vaccine group, mycobacterial bacilli were identified extracellularly within the center of caseating granulomas, with relatively equal proportions of B- and T-lymphocytes maintained across both early and late times. Despite the differences in granuloma-specific lymphocyte recruitment, markers for cell-mediated immunity (e.g., IFN-γ release) were robust in both injected pgsN and inactivated vaccine groups. In contrast, the intranasal live-attenuated vaccine did not elicit any reaction at site of inoculation, nor cell-mediated immune responses. Finally, 80% of animals in the inactivated vaccine group significantly reacted to purified protein derivatives from M. bovis, while reactivity was detected in only 20% of animals receiving pgsN vaccine, suggesting a higher level of cross reactivity for bovine tuberculosis when inactivated vaccine is used. Overall, these results depict the cellular recruitment strategies driving immune responses elicited by both live-attenuated and inactivated vaccines that target Johne's disease. Frontiers Media S.A. 2023-01-09 /pmc/articles/PMC9868903/ /pubmed/36699320 http://dx.doi.org/10.3389/fvets.2022.1046704 Text en Copyright © 2023 Hanafy, Hansen, Phanse, Wu, Nelson, Aschenbroich and Talaat. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Hanafy, Mostafa
Hansen, Chungyi
Phanse, Yashdeep
Wu, Chia-wei
Nelson, Kathryn
Aschenbroich, Sophie A.
Talaat, Adel M.
Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats
title Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats
title_full Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats
title_fullStr Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats
title_full_unstemmed Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats
title_short Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats
title_sort characterization of early immune responses elicited by live and inactivated vaccines against johne's disease in goats
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868903/
https://www.ncbi.nlm.nih.gov/pubmed/36699320
http://dx.doi.org/10.3389/fvets.2022.1046704
work_keys_str_mv AT hanafymostafa characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats
AT hansenchungyi characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats
AT phanseyashdeep characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats
AT wuchiawei characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats
AT nelsonkathryn characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats
AT aschenbroichsophiea characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats
AT talaatadelm characterizationofearlyimmuneresponseselicitedbyliveandinactivatedvaccinesagainstjohnesdiseaseingoats