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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2022.1046704/full |
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| author | Mostafa Hanafy Mostafa Hanafy Chungyi Hansen Yashdeep Phanse Chia-wei Wu Kathryn Nelson Sophie A. Aschenbroich Adel M. Talaat Adel M. Talaat |
| author_facet | Mostafa Hanafy Mostafa Hanafy Chungyi Hansen Yashdeep Phanse Chia-wei Wu Kathryn Nelson Sophie A. Aschenbroich Adel M. Talaat Adel M. Talaat |
| author_sort | Mostafa Hanafy |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T23:57:12Z |
| format | Article |
| id | doaj.art-dae926b2d95b4f3bb349ebbcd08f2032 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-04-10T23:57:12Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-dae926b2d95b4f3bb349ebbcd08f20322023-01-10T12:50:30ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-01-01910.3389/fvets.2022.10467041046704Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goatsMostafa Hanafy0Mostafa Hanafy1Chungyi Hansen2Yashdeep Phanse3Chia-wei Wu4Kathryn Nelson5Sophie A. Aschenbroich6Adel M. Talaat7Adel M. Talaat8Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United StatesDepartment of Microbiology and Immunology, Faculty of Veterinary Medicine, Cairo University, Giza, EgyptDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United StatesPan Genome Systems, Madison, WI, United StatesDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United StatesResearch Animal Resources Center, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United StatesDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United StatesPan Genome Systems, Madison, WI, United StatesMycobacterium 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.https://www.frontiersin.org/articles/10.3389/fvets.2022.1046704/fullparatuberculosis (MAP)Johne's diseasevaccineimmunitylive vaccineinactivated vaccine |
| spellingShingle | Mostafa Hanafy Mostafa Hanafy Chungyi Hansen Yashdeep Phanse Chia-wei Wu Kathryn Nelson Sophie A. Aschenbroich Adel M. Talaat Adel M. Talaat Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats Frontiers in Veterinary Science paratuberculosis (MAP) Johne's disease vaccine immunity live vaccine inactivated vaccine |
| 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 | paratuberculosis (MAP) Johne's disease vaccine immunity live vaccine inactivated vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2022.1046704/full |
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