Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis
Bovine tuberculosis (BTB) caused by Mycobacterium bovis remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain...
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| Veröffentlicht in: | Scientific reports 2019-11, Vol.9 (1), p.17791, Article 17791 |
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| creator | Chandran, Aneesh Williams, Kerstin Mendum, Tom Stewart, Graham Clark, Simon Zadi, Sirine Lanni, Faye McLeod, Neil Williams, Ann Villarreal-Ramos, Bernardo Vordermeier, Martin Maroudam, Veerasamy Prasad, Aravind Bharti, Neeraj Banerjee, Ruma Manjari Kasibhatla, Sunitha McFadden, Johnjoe |
| description | Bovine tuberculosis (BTB) caused by
Mycobacterium bovis
remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the
M. bovis
pathogen, BCG, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the PPD test. Diagnostic tests capable of Differentiating Infected from Vaccinated Animals (DIVA) have been developed that detect immune responses to
M. bovis
antigens absent in BCG; but these are too expensive and insufficiently sensitive to be used for BTB control worldwide. To address these problems we aimed to generate a synergistic vaccine and diagnostic approach that would permit the vaccination of cattle without interfering with the conventional PPD-based surveillance. The approach was to widen the pool of
M. bovis
antigens that could be used as DIVA targets, by identifying antigenic proteins that could be deleted from BCG without affecting the persistence and protective efficacy of the vaccine in cattle. Using transposon mutagenesis we identified genes that were essential and those that were non-essential for persistence in bovine lymph nodes. We then inactivated selected immunogenic, but non-essential genes in BCG Danish to create a diagnostic-compatible triple knock-out ΔBCG TK strain. The protective efficacy of the ΔBCG TK was tested in guinea pigs experimentally infected with
M. bovis
by aerosol and found to be equivalent to wild-type BCG. A complementary diagnostic skin test was developed with the antigenic proteins encoded by the deleted genes which did not cross-react in vaccinated or in uninfected guinea pigs. This study demonstrates the functionality of a new and improved BCG strain which retains its protective efficacy but is diagnostically compatible with a novel DIVA skin test that could be implemented in control programmes. |
| doi_str_mv | 10.1038/s41598-019-54108-y |
| format | Article |
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Mycobacterium bovis
remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the
M. bovis
pathogen, BCG, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the PPD test. Diagnostic tests capable of Differentiating Infected from Vaccinated Animals (DIVA) have been developed that detect immune responses to
M. bovis
antigens absent in BCG; but these are too expensive and insufficiently sensitive to be used for BTB control worldwide. To address these problems we aimed to generate a synergistic vaccine and diagnostic approach that would permit the vaccination of cattle without interfering with the conventional PPD-based surveillance. The approach was to widen the pool of
M. bovis
antigens that could be used as DIVA targets, by identifying antigenic proteins that could be deleted from BCG without affecting the persistence and protective efficacy of the vaccine in cattle. Using transposon mutagenesis we identified genes that were essential and those that were non-essential for persistence in bovine lymph nodes. We then inactivated selected immunogenic, but non-essential genes in BCG Danish to create a diagnostic-compatible triple knock-out ΔBCG TK strain. The protective efficacy of the ΔBCG TK was tested in guinea pigs experimentally infected with
M. bovis
by aerosol and found to be equivalent to wild-type BCG. A complementary diagnostic skin test was developed with the antigenic proteins encoded by the deleted genes which did not cross-react in vaccinated or in uninfected guinea pigs. This study demonstrates the functionality of a new and improved BCG strain which retains its protective efficacy but is diagnostically compatible with a novel DIVA skin test that could be implemented in control programmes.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-54108-y</identifier><identifier>PMID: 31780694</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 38/22 ; 38/23 ; 38/77 ; 45/29 ; 45/41 ; 45/70 ; 631/326/2521 ; 631/326/590/1867 ; 96/109 ; 96/44 ; Animals ; Antigens ; Bacillus Calmette-Guerin vaccine ; BCG ; BCG Vaccine - genetics ; BCG Vaccine - immunology ; Cattle ; Cross Reactions ; Developing countries ; Gene Knockout Techniques ; Guinea Pigs ; Humanities and Social Sciences ; Immune response ; Immunization ; Immunogenicity ; LDCs ; Lymph nodes ; Macrophages - metabolism ; Macrophages - microbiology ; multidisciplinary ; Mycobacterium bovis - genetics ; Mycobacterium bovis - immunology ; Science ; Science (multidisciplinary) ; Skin tests ; Transduction, Genetic ; Transposon mutagenesis ; Tuberculin ; Tuberculin - genetics ; Tuberculin - immunology ; Tuberculin Test ; Tuberculosis ; Tuberculosis - diagnosis ; Tuberculosis - microbiology ; Tuberculosis - veterinary ; Tuberculosis, Bovine - diagnosis ; Tuberculosis, Bovine - microbiology ; Vaccination ; Vaccines ; Vaccines, Attenuated - immunology</subject><ispartof>Scientific reports, 2019-11, Vol.9 (1), p.17791, Article 17791</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-ef87e8b229d3de209782a667eefe6c1224107e4a2796bc9dfb11ad361e6fe8d03</citedby><cites>FETCH-LOGICAL-c540t-ef87e8b229d3de209782a667eefe6c1224107e4a2796bc9dfb11ad361e6fe8d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882907/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882907/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31780694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chandran, Aneesh</creatorcontrib><creatorcontrib>Williams, Kerstin</creatorcontrib><creatorcontrib>Mendum, Tom</creatorcontrib><creatorcontrib>Stewart, Graham</creatorcontrib><creatorcontrib>Clark, Simon</creatorcontrib><creatorcontrib>Zadi, Sirine</creatorcontrib><creatorcontrib>Lanni, Faye</creatorcontrib><creatorcontrib>McLeod, Neil</creatorcontrib><creatorcontrib>Williams, Ann</creatorcontrib><creatorcontrib>Villarreal-Ramos, Bernardo</creatorcontrib><creatorcontrib>Vordermeier, Martin</creatorcontrib><creatorcontrib>Maroudam, Veerasamy</creatorcontrib><creatorcontrib>Prasad, Aravind</creatorcontrib><creatorcontrib>Bharti, Neeraj</creatorcontrib><creatorcontrib>Banerjee, Ruma</creatorcontrib><creatorcontrib>Manjari Kasibhatla, Sunitha</creatorcontrib><creatorcontrib>McFadden, Johnjoe</creatorcontrib><title>Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Bovine tuberculosis (BTB) caused by
Mycobacterium bovis
remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the
M. bovis
pathogen, BCG, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the PPD test. Diagnostic tests capable of Differentiating Infected from Vaccinated Animals (DIVA) have been developed that detect immune responses to
M. bovis
antigens absent in BCG; but these are too expensive and insufficiently sensitive to be used for BTB control worldwide. To address these problems we aimed to generate a synergistic vaccine and diagnostic approach that would permit the vaccination of cattle without interfering with the conventional PPD-based surveillance. The approach was to widen the pool of
M. bovis
antigens that could be used as DIVA targets, by identifying antigenic proteins that could be deleted from BCG without affecting the persistence and protective efficacy of the vaccine in cattle. Using transposon mutagenesis we identified genes that were essential and those that were non-essential for persistence in bovine lymph nodes. We then inactivated selected immunogenic, but non-essential genes in BCG Danish to create a diagnostic-compatible triple knock-out ΔBCG TK strain. The protective efficacy of the ΔBCG TK was tested in guinea pigs experimentally infected with
M. bovis
by aerosol and found to be equivalent to wild-type BCG. A complementary diagnostic skin test was developed with the antigenic proteins encoded by the deleted genes which did not cross-react in vaccinated or in uninfected guinea pigs. This study demonstrates the functionality of a new and improved BCG strain which retains its protective efficacy but is diagnostically compatible with a novel DIVA skin test that could be implemented in control programmes.</description><subject>13/106</subject><subject>38/22</subject><subject>38/23</subject><subject>38/77</subject><subject>45/29</subject><subject>45/41</subject><subject>45/70</subject><subject>631/326/2521</subject><subject>631/326/590/1867</subject><subject>96/109</subject><subject>96/44</subject><subject>Animals</subject><subject>Antigens</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>BCG</subject><subject>BCG Vaccine - genetics</subject><subject>BCG Vaccine - immunology</subject><subject>Cattle</subject><subject>Cross Reactions</subject><subject>Developing countries</subject><subject>Gene Knockout Techniques</subject><subject>Guinea Pigs</subject><subject>Humanities and Social Sciences</subject><subject>Immune response</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>LDCs</subject><subject>Lymph nodes</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - microbiology</subject><subject>multidisciplinary</subject><subject>Mycobacterium bovis - genetics</subject><subject>Mycobacterium bovis - immunology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Skin tests</subject><subject>Transduction, Genetic</subject><subject>Transposon mutagenesis</subject><subject>Tuberculin</subject><subject>Tuberculin - genetics</subject><subject>Tuberculin - immunology</subject><subject>Tuberculin Test</subject><subject>Tuberculosis</subject><subject>Tuberculosis - diagnosis</subject><subject>Tuberculosis - microbiology</subject><subject>Tuberculosis - veterinary</subject><subject>Tuberculosis, Bovine - diagnosis</subject><subject>Tuberculosis, Bovine - microbiology</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, Attenuated - immunology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UUFOwzAQtBCIVqUf4IAicQ7YjpPYFyQoUJAquMDZcpxNcZXGxU4q9fe4pJRywZe1tbMz4x2Ezgm-Ijjh156RVPAYExGnjGAeb47QkGKWxjSh9PjgPkBj7xc4nJQKRsQpGiQk5zgTbIhe7mENtV0toWkjW0UqKo2aN9a3RkfaLleqNUUN0d1kGq2V1qaBSM2VaXwb3dn19tl2BTjd1dYbf4ZOKlV7GO_qCL0_PrxNnuLZ6_R5cjuLdcpwG0PFc-AFpaJMSqBY5JyqLMsBKsg0oTT8KAemaC6yQouyKghRZZIRyCrgJU5G6KbnXXXFEkod3DtVy5UzS-U20ioj_3Ya8yHndi0zzqnAeSC43BE4-9mBb-XCdq4JniVNiGCcMr6VoT1KO-u9g2qvQLDcxiD7GGSIQX7HIDdh6OLQ237kZ-kBkPQAH1rNHNyv9j-0X2-9lPo</recordid><startdate>20191128</startdate><enddate>20191128</enddate><creator>Chandran, Aneesh</creator><creator>Williams, Kerstin</creator><creator>Mendum, Tom</creator><creator>Stewart, Graham</creator><creator>Clark, Simon</creator><creator>Zadi, Sirine</creator><creator>Lanni, Faye</creator><creator>McLeod, Neil</creator><creator>Williams, Ann</creator><creator>Villarreal-Ramos, Bernardo</creator><creator>Vordermeier, Martin</creator><creator>Maroudam, Veerasamy</creator><creator>Prasad, Aravind</creator><creator>Bharti, Neeraj</creator><creator>Banerjee, Ruma</creator><creator>Manjari Kasibhatla, Sunitha</creator><creator>McFadden, Johnjoe</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20191128</creationdate><title>Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis</title><author>Chandran, Aneesh ; Williams, Kerstin ; Mendum, Tom ; Stewart, Graham ; Clark, Simon ; Zadi, Sirine ; Lanni, Faye ; McLeod, Neil ; Williams, Ann ; Villarreal-Ramos, Bernardo ; Vordermeier, Martin ; Maroudam, Veerasamy ; Prasad, Aravind ; Bharti, Neeraj ; Banerjee, Ruma ; Manjari Kasibhatla, Sunitha ; McFadden, Johnjoe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-ef87e8b229d3de209782a667eefe6c1224107e4a2796bc9dfb11ad361e6fe8d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/106</topic><topic>38/22</topic><topic>38/23</topic><topic>38/77</topic><topic>45/29</topic><topic>45/41</topic><topic>45/70</topic><topic>631/326/2521</topic><topic>631/326/590/1867</topic><topic>96/109</topic><topic>96/44</topic><topic>Animals</topic><topic>Antigens</topic><topic>Bacillus Calmette-Guerin vaccine</topic><topic>BCG</topic><topic>BCG Vaccine - 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veterinary</topic><topic>Tuberculosis, Bovine - diagnosis</topic><topic>Tuberculosis, Bovine - microbiology</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vaccines, Attenuated - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chandran, Aneesh</creatorcontrib><creatorcontrib>Williams, Kerstin</creatorcontrib><creatorcontrib>Mendum, Tom</creatorcontrib><creatorcontrib>Stewart, Graham</creatorcontrib><creatorcontrib>Clark, Simon</creatorcontrib><creatorcontrib>Zadi, Sirine</creatorcontrib><creatorcontrib>Lanni, Faye</creatorcontrib><creatorcontrib>McLeod, Neil</creatorcontrib><creatorcontrib>Williams, Ann</creatorcontrib><creatorcontrib>Villarreal-Ramos, Bernardo</creatorcontrib><creatorcontrib>Vordermeier, Martin</creatorcontrib><creatorcontrib>Maroudam, Veerasamy</creatorcontrib><creatorcontrib>Prasad, Aravind</creatorcontrib><creatorcontrib>Bharti, Neeraj</creatorcontrib><creatorcontrib>Banerjee, Ruma</creatorcontrib><creatorcontrib>Manjari Kasibhatla, Sunitha</creatorcontrib><creatorcontrib>McFadden, Johnjoe</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</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>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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chandran, Aneesh</au><au>Williams, Kerstin</au><au>Mendum, Tom</au><au>Stewart, Graham</au><au>Clark, Simon</au><au>Zadi, Sirine</au><au>Lanni, Faye</au><au>McLeod, Neil</au><au>Williams, Ann</au><au>Villarreal-Ramos, Bernardo</au><au>Vordermeier, Martin</au><au>Maroudam, Veerasamy</au><au>Prasad, Aravind</au><au>Bharti, Neeraj</au><au>Banerjee, Ruma</au><au>Manjari Kasibhatla, Sunitha</au><au>McFadden, Johnjoe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-11-28</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>17791</spage><pages>17791-</pages><artnum>17791</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Bovine tuberculosis (BTB) caused by
Mycobacterium bovis
remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the
M. bovis
pathogen, BCG, is not used to control bovine tuberculosis in cattle at present, due to its variable efficacy and because it interferes with the PPD test. Diagnostic tests capable of Differentiating Infected from Vaccinated Animals (DIVA) have been developed that detect immune responses to
M. bovis
antigens absent in BCG; but these are too expensive and insufficiently sensitive to be used for BTB control worldwide. To address these problems we aimed to generate a synergistic vaccine and diagnostic approach that would permit the vaccination of cattle without interfering with the conventional PPD-based surveillance. The approach was to widen the pool of
M. bovis
antigens that could be used as DIVA targets, by identifying antigenic proteins that could be deleted from BCG without affecting the persistence and protective efficacy of the vaccine in cattle. Using transposon mutagenesis we identified genes that were essential and those that were non-essential for persistence in bovine lymph nodes. We then inactivated selected immunogenic, but non-essential genes in BCG Danish to create a diagnostic-compatible triple knock-out ΔBCG TK strain. The protective efficacy of the ΔBCG TK was tested in guinea pigs experimentally infected with
M. bovis
by aerosol and found to be equivalent to wild-type BCG. A complementary diagnostic skin test was developed with the antigenic proteins encoded by the deleted genes which did not cross-react in vaccinated or in uninfected guinea pigs. This study demonstrates the functionality of a new and improved BCG strain which retains its protective efficacy but is diagnostically compatible with a novel DIVA skin test that could be implemented in control programmes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31780694</pmid><doi>10.1038/s41598-019-54108-y</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2019-11, Vol.9 (1), p.17791, Article 17791 |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 13/106 38/22 38/23 38/77 45/29 45/41 45/70 631/326/2521 631/326/590/1867 96/109 96/44 Animals Antigens Bacillus Calmette-Guerin vaccine BCG BCG Vaccine - genetics BCG Vaccine - immunology Cattle Cross Reactions Developing countries Gene Knockout Techniques Guinea Pigs Humanities and Social Sciences Immune response Immunization Immunogenicity LDCs Lymph nodes Macrophages - metabolism Macrophages - microbiology multidisciplinary Mycobacterium bovis - genetics Mycobacterium bovis - immunology Science Science (multidisciplinary) Skin tests Transduction, Genetic Transposon mutagenesis Tuberculin Tuberculin - genetics Tuberculin - immunology Tuberculin Test Tuberculosis Tuberculosis - diagnosis Tuberculosis - microbiology Tuberculosis - veterinary Tuberculosis, Bovine - diagnosis Tuberculosis, Bovine - microbiology Vaccination Vaccines Vaccines, Attenuated - immunology |
| title | Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T09%3A58%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20of%20a%20diagnostic%20compatible%20BCG%20vaccine%20against%20Bovine%20tuberculosis&rft.jtitle=Scientific%20reports&rft.au=Chandran,%20Aneesh&rft.date=2019-11-28&rft.volume=9&rft.issue=1&rft.spage=17791&rft.pages=17791-&rft.artnum=17791&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-019-54108-y&rft_dat=%3Cproquest_pubme%3E2319482480%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2319482480&rft_id=info:pmid/31780694&rfr_iscdi=true |