Evaluation of a virulent strain of Mycobacterium avium subsp. Paratuberculosis used as a heat-killed vaccine
•Our vaccine candidate (6611 strain) reduced the infection in challenged mice.•Our vaccine candidate induced humoral and cellular immune response.•No false PPDb reactor was detected in the caudal fold tuberculin test. Bovine paratuberculosis is one of the most important chronic infectious diseases i...
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| Veröffentlicht in: | Vaccine 2021-12, Vol.39 (51), p.7401-7412 |
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| creator | Colombatti Olivieri, María Alejandra Moyano, Roberto Damián Mon, María Laura Gravisaco, María José Alvarado Pinedo, María Fiorella Delgado, Fernando Oscar Hernández Pando, Rogelio Alonso, María Natalia Cuerda, María Ximena Santangelo, María de la Paz Romano, María Isabel |
| description | •Our vaccine candidate (6611 strain) reduced the infection in challenged mice.•Our vaccine candidate induced humoral and cellular immune response.•No false PPDb reactor was detected in the caudal fold tuberculin test.
Bovine paratuberculosis is one of the most important chronic infectious diseases in livestock. This disease is difficult to control because of its inefficient management (test and cull strategy and inadequate biosecurity). Thus, the development of an effective vaccine is essential. In this study, we evaluated a local virulent strain (6611) of Mycobacterium avium subsp. paratuberculosis as an inactivated vaccine in comparison with the Silirum vaccine in mouse model and cattle. Regarding the mice model, only the groups vaccinated with 6611 showed lower colony forming unit (CFU) counts with a lower lesion score in the liver in comparison to the control group at 6 and 12 weeks post-challenge (wpc). The immune response was predominantly humoral (IgG1), although both vaccinated groups presented a cellular response with IFNγ production as well, but the 6611 group had also significant production of IL-2, IL-6, IL-17a, TNF, and IL-10. In cattle, the 6611 vaccinated group was the only one that maintained significant antibody values at the end of the trial, with significant production of IgG2 and IFNγ. No PPDb reactor was detected in the vaccinated animals, according to the intradermal caudal fold tuberculin test. Our results indicate that the 6611 local strain protected mice from challenge with a virulent strain, by inducing a humoral and cellular immune response. In the bovine, the natural host, the evaluated vaccine also induced humoral and cellular immune responses, with higher levels of CD4 + CD25+ and CD8 + CD25+ T cells populations than the commercial vaccine. Despite the encouraging results obtained in this study, an experimental challenge trial in cattle is mandatory to evaluate the efficacy of our candidate vaccine in the main host. |
| doi_str_mv | 10.1016/j.vaccine.2021.10.084 |
| format | Article |
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Bovine paratuberculosis is one of the most important chronic infectious diseases in livestock. This disease is difficult to control because of its inefficient management (test and cull strategy and inadequate biosecurity). Thus, the development of an effective vaccine is essential. In this study, we evaluated a local virulent strain (6611) of Mycobacterium avium subsp. paratuberculosis as an inactivated vaccine in comparison with the Silirum vaccine in mouse model and cattle. Regarding the mice model, only the groups vaccinated with 6611 showed lower colony forming unit (CFU) counts with a lower lesion score in the liver in comparison to the control group at 6 and 12 weeks post-challenge (wpc). The immune response was predominantly humoral (IgG1), although both vaccinated groups presented a cellular response with IFNγ production as well, but the 6611 group had also significant production of IL-2, IL-6, IL-17a, TNF, and IL-10. In cattle, the 6611 vaccinated group was the only one that maintained significant antibody values at the end of the trial, with significant production of IgG2 and IFNγ. No PPDb reactor was detected in the vaccinated animals, according to the intradermal caudal fold tuberculin test. Our results indicate that the 6611 local strain protected mice from challenge with a virulent strain, by inducing a humoral and cellular immune response. In the bovine, the natural host, the evaluated vaccine also induced humoral and cellular immune responses, with higher levels of CD4 + CD25+ and CD8 + CD25+ T cells populations than the commercial vaccine. Despite the encouraging results obtained in this study, an experimental challenge trial in cattle is mandatory to evaluate the efficacy of our candidate vaccine in the main host.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2021.10.084</identifier><identifier>PMID: 34774361</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animal diseases ; Animals ; Antibodies ; Bacterial Vaccines ; Biosecurity ; Cattle ; Cattle Diseases - prevention & control ; CD25 antigen ; CD4 antigen ; CD8 antigen ; Cytokines ; Disease control ; Disease prevention ; Granulomas ; Histopathology ; Hot Temperature ; Immune response ; Immune response (cell-mediated) ; Immune response (humoral) ; Immune system ; Immunoglobulin G ; Infections ; Infectious diseases ; Interleukin 10 ; Interleukin 2 ; Interleukin 6 ; Livestock ; Lymphocytes ; Lymphocytes T ; Mice ; Mycobacterium avium ; Mycobacterium avium subsp. paratuberculosis ; Paratuberculosis ; Paratuberculosis - prevention & control ; Silirum ; Tuberculin ; Tuberculosis ; Tumor necrosis factor ; Vaccine ; Vaccines ; Vaccines, Inactivated ; Virulence ; γ-Interferon</subject><ispartof>Vaccine, 2021-12, Vol.39 (51), p.7401-7412</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>2021. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-79eaf26357362a135c3dc3e0244d588debae1d63a7c0ada5245222806ac34da93</citedby><cites>FETCH-LOGICAL-c393t-79eaf26357362a135c3dc3e0244d588debae1d63a7c0ada5245222806ac34da93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2608446500?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34774361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Colombatti Olivieri, María Alejandra</creatorcontrib><creatorcontrib>Moyano, Roberto Damián</creatorcontrib><creatorcontrib>Mon, María Laura</creatorcontrib><creatorcontrib>Gravisaco, María José</creatorcontrib><creatorcontrib>Alvarado Pinedo, María Fiorella</creatorcontrib><creatorcontrib>Delgado, Fernando Oscar</creatorcontrib><creatorcontrib>Hernández Pando, Rogelio</creatorcontrib><creatorcontrib>Alonso, María Natalia</creatorcontrib><creatorcontrib>Cuerda, María Ximena</creatorcontrib><creatorcontrib>Santangelo, María de la Paz</creatorcontrib><creatorcontrib>Romano, María Isabel</creatorcontrib><title>Evaluation of a virulent strain of Mycobacterium avium subsp. Paratuberculosis used as a heat-killed vaccine</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•Our vaccine candidate (6611 strain) reduced the infection in challenged mice.•Our vaccine candidate induced humoral and cellular immune response.•No false PPDb reactor was detected in the caudal fold tuberculin test.
Bovine paratuberculosis is one of the most important chronic infectious diseases in livestock. This disease is difficult to control because of its inefficient management (test and cull strategy and inadequate biosecurity). Thus, the development of an effective vaccine is essential. In this study, we evaluated a local virulent strain (6611) of Mycobacterium avium subsp. paratuberculosis as an inactivated vaccine in comparison with the Silirum vaccine in mouse model and cattle. Regarding the mice model, only the groups vaccinated with 6611 showed lower colony forming unit (CFU) counts with a lower lesion score in the liver in comparison to the control group at 6 and 12 weeks post-challenge (wpc). The immune response was predominantly humoral (IgG1), although both vaccinated groups presented a cellular response with IFNγ production as well, but the 6611 group had also significant production of IL-2, IL-6, IL-17a, TNF, and IL-10. In cattle, the 6611 vaccinated group was the only one that maintained significant antibody values at the end of the trial, with significant production of IgG2 and IFNγ. No PPDb reactor was detected in the vaccinated animals, according to the intradermal caudal fold tuberculin test. Our results indicate that the 6611 local strain protected mice from challenge with a virulent strain, by inducing a humoral and cellular immune response. In the bovine, the natural host, the evaluated vaccine also induced humoral and cellular immune responses, with higher levels of CD4 + CD25+ and CD8 + CD25+ T cells populations than the commercial vaccine. Despite the encouraging results obtained in this study, an experimental challenge trial in cattle is mandatory to evaluate the efficacy of our candidate vaccine in the main host.</description><subject>Animal diseases</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Bacterial Vaccines</subject><subject>Biosecurity</subject><subject>Cattle</subject><subject>Cattle Diseases - prevention & control</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cytokines</subject><subject>Disease control</subject><subject>Disease prevention</subject><subject>Granulomas</subject><subject>Histopathology</subject><subject>Hot Temperature</subject><subject>Immune response</subject><subject>Immune response (cell-mediated)</subject><subject>Immune response (humoral)</subject><subject>Immune system</subject><subject>Immunoglobulin G</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interleukin 10</subject><subject>Interleukin 2</subject><subject>Interleukin 6</subject><subject>Livestock</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mycobacterium avium</subject><subject>Mycobacterium avium subsp. paratuberculosis</subject><subject>Paratuberculosis</subject><subject>Paratuberculosis - prevention & control</subject><subject>Silirum</subject><subject>Tuberculin</subject><subject>Tuberculosis</subject><subject>Tumor necrosis factor</subject><subject>Vaccine</subject><subject>Vaccines</subject><subject>Vaccines, Inactivated</subject><subject>Virulence</subject><subject>γ-Interferon</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkc2KFDEUhYMoTs_oIygFbmZTZf5TtRIZxlEY0YWCu3AruY1p01VtUimYtzdtty7cuEng8J2Tm3MJecFoxyjTr3fdCs6FCTtOOataR3v5iGxYb0TLFesfkw3lWraS0W8X5DLnHaVUCTY8JRdCGiOFZhsSb1eIBZYwT828baBZQyoRp6XJS4LwW_z44OYR3IIplH0D6_HMZcyHrvkMCZYyYnIlzjnkpmT0DeQa9B1haX-EGKtwHvUZebKFmPH5-b4iX9_dfrl5395_uvtw8_a-dWIQS2sGhC3XQhmhOTChnPBOIOVSetX3HkdA5rUA4yh4UFwqznlPNTghPQziilyfcg9p_lkwL3YfssMYYcK5ZMvVYMww6MFU9NU_6G4uaarTWa5ro1IrSiulTpRLc84Jt_aQwh7Sg2XUHtdhd_b8R3tcx1Gu5up7eU4v4x79X9ef_ivw5gRgrWMNmGx2ASeHPiR0i_Vz-M8TvwC_qp6Z</recordid><startdate>20211217</startdate><enddate>20211217</enddate><creator>Colombatti Olivieri, María Alejandra</creator><creator>Moyano, Roberto Damián</creator><creator>Mon, María Laura</creator><creator>Gravisaco, María José</creator><creator>Alvarado Pinedo, María Fiorella</creator><creator>Delgado, Fernando Oscar</creator><creator>Hernández Pando, Rogelio</creator><creator>Alonso, María Natalia</creator><creator>Cuerda, María Ximena</creator><creator>Santangelo, María de la Paz</creator><creator>Romano, María Isabel</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20211217</creationdate><title>Evaluation of a virulent strain of Mycobacterium avium subsp. Paratuberculosis used as a heat-killed vaccine</title><author>Colombatti Olivieri, María Alejandra ; Moyano, Roberto Damián ; Mon, María Laura ; Gravisaco, María José ; Alvarado Pinedo, María Fiorella ; Delgado, Fernando Oscar ; Hernández Pando, Rogelio ; Alonso, María Natalia ; Cuerda, María Ximena ; Santangelo, María de la Paz ; Romano, María Isabel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-79eaf26357362a135c3dc3e0244d588debae1d63a7c0ada5245222806ac34da93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animal diseases</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Bacterial Vaccines</topic><topic>Biosecurity</topic><topic>Cattle</topic><topic>Cattle Diseases - prevention & control</topic><topic>CD25 antigen</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cytokines</topic><topic>Disease control</topic><topic>Disease prevention</topic><topic>Granulomas</topic><topic>Histopathology</topic><topic>Hot Temperature</topic><topic>Immune response</topic><topic>Immune response (cell-mediated)</topic><topic>Immune response (humoral)</topic><topic>Immune system</topic><topic>Immunoglobulin G</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Interleukin 10</topic><topic>Interleukin 2</topic><topic>Interleukin 6</topic><topic>Livestock</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mycobacterium avium</topic><topic>Mycobacterium avium subsp. paratuberculosis</topic><topic>Paratuberculosis</topic><topic>Paratuberculosis - prevention & control</topic><topic>Silirum</topic><topic>Tuberculin</topic><topic>Tuberculosis</topic><topic>Tumor necrosis factor</topic><topic>Vaccine</topic><topic>Vaccines</topic><topic>Vaccines, Inactivated</topic><topic>Virulence</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Colombatti Olivieri, María Alejandra</creatorcontrib><creatorcontrib>Moyano, Roberto Damián</creatorcontrib><creatorcontrib>Mon, María Laura</creatorcontrib><creatorcontrib>Gravisaco, María José</creatorcontrib><creatorcontrib>Alvarado Pinedo, María Fiorella</creatorcontrib><creatorcontrib>Delgado, Fernando Oscar</creatorcontrib><creatorcontrib>Hernández Pando, Rogelio</creatorcontrib><creatorcontrib>Alonso, María Natalia</creatorcontrib><creatorcontrib>Cuerda, María Ximena</creatorcontrib><creatorcontrib>Santangelo, María de la Paz</creatorcontrib><creatorcontrib>Romano, María Isabel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - 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Paratuberculosis used as a heat-killed vaccine</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2021-12-17</date><risdate>2021</risdate><volume>39</volume><issue>51</issue><spage>7401</spage><epage>7412</epage><pages>7401-7412</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•Our vaccine candidate (6611 strain) reduced the infection in challenged mice.•Our vaccine candidate induced humoral and cellular immune response.•No false PPDb reactor was detected in the caudal fold tuberculin test.
Bovine paratuberculosis is one of the most important chronic infectious diseases in livestock. This disease is difficult to control because of its inefficient management (test and cull strategy and inadequate biosecurity). Thus, the development of an effective vaccine is essential. In this study, we evaluated a local virulent strain (6611) of Mycobacterium avium subsp. paratuberculosis as an inactivated vaccine in comparison with the Silirum vaccine in mouse model and cattle. Regarding the mice model, only the groups vaccinated with 6611 showed lower colony forming unit (CFU) counts with a lower lesion score in the liver in comparison to the control group at 6 and 12 weeks post-challenge (wpc). The immune response was predominantly humoral (IgG1), although both vaccinated groups presented a cellular response with IFNγ production as well, but the 6611 group had also significant production of IL-2, IL-6, IL-17a, TNF, and IL-10. In cattle, the 6611 vaccinated group was the only one that maintained significant antibody values at the end of the trial, with significant production of IgG2 and IFNγ. No PPDb reactor was detected in the vaccinated animals, according to the intradermal caudal fold tuberculin test. Our results indicate that the 6611 local strain protected mice from challenge with a virulent strain, by inducing a humoral and cellular immune response. In the bovine, the natural host, the evaluated vaccine also induced humoral and cellular immune responses, with higher levels of CD4 + CD25+ and CD8 + CD25+ T cells populations than the commercial vaccine. Despite the encouraging results obtained in this study, an experimental challenge trial in cattle is mandatory to evaluate the efficacy of our candidate vaccine in the main host.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>34774361</pmid><doi>10.1016/j.vaccine.2021.10.084</doi><tpages>12</tpages></addata></record> |
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| subjects | Animal diseases Animals Antibodies Bacterial Vaccines Biosecurity Cattle Cattle Diseases - prevention & control CD25 antigen CD4 antigen CD8 antigen Cytokines Disease control Disease prevention Granulomas Histopathology Hot Temperature Immune response Immune response (cell-mediated) Immune response (humoral) Immune system Immunoglobulin G Infections Infectious diseases Interleukin 10 Interleukin 2 Interleukin 6 Livestock Lymphocytes Lymphocytes T Mice Mycobacterium avium Mycobacterium avium subsp. paratuberculosis Paratuberculosis Paratuberculosis - prevention & control Silirum Tuberculin Tuberculosis Tumor necrosis factor Vaccine Vaccines Vaccines, Inactivated Virulence γ-Interferon |
| title | Evaluation of a virulent strain of Mycobacterium avium subsp. Paratuberculosis used as a heat-killed vaccine |
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