MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques
Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to...
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| Veröffentlicht in: | PloS one 2009-04, Vol.4 (4), p.e5264-e5264 |
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| creator | Verreck, Frank A W Vervenne, Richard A W Kondova, Ivanela van Kralingen, Klaas W Remarque, Edmond J Braskamp, Gerco van der Werff, Nicole M Kersbergen, Ariena Ottenhoff, Tom H M Heidt, Peter J Gilbert, Sarah C Gicquel, Brigitte Hill, Adrian V S Martin, Carlos McShane, Helen Thomas, Alan W |
| description | Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection.
Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A), and attenuated M. tuberculosis with a disrupted phoP gene (SO2) as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG) and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht) as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60).
Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates. |
| doi_str_mv | 10.1371/journal.pone.0005264 |
| format | Article |
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Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A), and attenuated M. tuberculosis with a disrupted phoP gene (SO2) as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG) and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht) as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60).
Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005264</identifier><identifier>PMID: 19367339</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acyltransferases - immunology ; Animal sciences ; Animals ; Antigens ; Antigens, Bacterial - immunology ; Attenuation ; Bacillus Calmette-Guerin vaccine ; Bacteria ; Bacterial Proteins - genetics ; BCG ; BCG Vaccine - immunology ; Biomarkers - blood ; Biosynthesis ; Body weight ; Body weight loss ; C-reactive protein ; Clinical trials ; Colony Count, Microbial ; Disease ; Effectiveness ; Genomes ; Health aspects ; Identification methods ; Immunogenicity ; Immunology ; Immunology/Immunity to Infections ; Infections ; Infectious Diseases ; Infectious Diseases/Bacterial Infections ; Infectious Diseases/Respiratory Infections ; Inflammation ; Inflammation - blood ; Interferon-gamma - secretion ; Lung - diagnostic imaging ; Lung - pathology ; Lungs ; Lymphocytes ; Macaca fascicularis ; Macaca mulatta ; Male ; Monkeys ; Monkeys & apes ; Mycobacterium bovis ; Mycobacterium bovis - immunology ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Parasitology ; Phylogeny ; Radiography ; Sulfur dioxide ; Treatment Outcome ; Tuberculosis ; Tuberculosis - immunology ; Tuberculosis - microbiology ; Tuberculosis - prevention & control ; Tuberculosis vaccines ; Tuberculosis Vaccines - immunology ; Vaccination ; Vaccine efficacy ; Vaccines ; Vaccines, Attenuated - immunology ; Vaccines, DNA - immunology ; Vaccinia virus ; Vaccinia virus - immunology ; Viruses ; Weight reduction ; Zoology ; γ-Interferon</subject><ispartof>PloS one, 2009-04, Vol.4 (4), p.e5264-e5264</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Verreck et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Verreck et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c721t-5dea70e2d826fa38ed6d91d3c4900717bd3ac53bc4ce5f7514c07491356e64423</citedby><cites>FETCH-LOGICAL-c721t-5dea70e2d826fa38ed6d91d3c4900717bd3ac53bc4ce5f7514c07491356e64423</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/PMC2666807/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666807/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19367339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Verreck, Frank A W</creatorcontrib><creatorcontrib>Vervenne, Richard A W</creatorcontrib><creatorcontrib>Kondova, Ivanela</creatorcontrib><creatorcontrib>van Kralingen, Klaas W</creatorcontrib><creatorcontrib>Remarque, Edmond J</creatorcontrib><creatorcontrib>Braskamp, Gerco</creatorcontrib><creatorcontrib>van der Werff, Nicole M</creatorcontrib><creatorcontrib>Kersbergen, Ariena</creatorcontrib><creatorcontrib>Ottenhoff, Tom H M</creatorcontrib><creatorcontrib>Heidt, Peter J</creatorcontrib><creatorcontrib>Gilbert, Sarah C</creatorcontrib><creatorcontrib>Gicquel, Brigitte</creatorcontrib><creatorcontrib>Hill, Adrian V S</creatorcontrib><creatorcontrib>Martin, Carlos</creatorcontrib><creatorcontrib>McShane, Helen</creatorcontrib><creatorcontrib>Thomas, Alan W</creatorcontrib><title>MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection.
Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A), and attenuated M. tuberculosis with a disrupted phoP gene (SO2) as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG) and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht) as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60).
Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates.</description><subject>Acyltransferases - immunology</subject><subject>Animal sciences</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antigens, Bacterial - immunology</subject><subject>Attenuation</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>Bacteria</subject><subject>Bacterial Proteins - genetics</subject><subject>BCG</subject><subject>BCG Vaccine - immunology</subject><subject>Biomarkers - blood</subject><subject>Biosynthesis</subject><subject>Body weight</subject><subject>Body weight loss</subject><subject>C-reactive protein</subject><subject>Clinical trials</subject><subject>Colony Count, Microbial</subject><subject>Disease</subject><subject>Effectiveness</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Identification methods</subject><subject>Immunogenicity</subject><subject>Immunology</subject><subject>Immunology/Immunity to Infections</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Infectious Diseases/Bacterial Infections</subject><subject>Infectious Diseases/Respiratory Infections</subject><subject>Inflammation</subject><subject>Inflammation - 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immunology</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccinia virus</subject><subject>Vaccinia virus - immunology</subject><subject>Viruses</subject><subject>Weight reduction</subject><subject>Zoology</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk39r1DAYx4sobk7fgWhAGAjemR9t0vwjnEPnYGPij_0bcsnTa0YvOZt0ulfi2zXnVV1loJTSkHy-3z75Jk9RPCZ4TpggLy_D0HvdzTfBwxxjXFFe3in2iWR0xilmd2-M94oHMV5mhtWc3y_28gIXjMn94vvZxWJeVwu0DCEm51coNOj10THS3uYX6ZTADzqBfYE2bXiPLDTOOPAJnc1RGpbQm6EL0UV0pY1xHrJTalFsw1e06UMCk9wVIGiyTJtrpFfa-ZimUudR30IcIlpro78MEB8W9xrdRXg0fg-Kz2_ffDp6Nzs9Pz45WpzOjKAkzSoLWmCgtqa80awGy60klplSYiyIWFqmTcWWpjRQNaIipcGilIRVHHhZUnZQPN35bnIlasw0KkIl5gLzTB4UJzvCBn2pNr1b6_5aBe3Uz4nQr5TukzMdKMpZ1UiNNTBaGiNrS3itpWwqmqtsWPZ6Nf5tWK7Bmhxjr7uJ6XTFu1atwlV25rzGIhscjgZ92MaU1NpFA12nPYQhKi4IpVLIf4IUV5KTqsrgs7_A20MYqZXO-3S-Cbk8s7VUi1IwynKBZabmt1D5sbB2Jt_TxuX5ieD5RJCZBN_SSg8xqpOPH_6fPb-Ysoc32BZ0l9oYuiG54OMULHeg6UOMPTS_z4JgtW2zX2mobZupsc2y7MnNc_wjGvuK_QCS_CLi</recordid><startdate>20090415</startdate><enddate>20090415</enddate><creator>Verreck, Frank A W</creator><creator>Vervenne, Richard A W</creator><creator>Kondova, Ivanela</creator><creator>van Kralingen, Klaas W</creator><creator>Remarque, Edmond J</creator><creator>Braskamp, Gerco</creator><creator>van der Werff, Nicole M</creator><creator>Kersbergen, Ariena</creator><creator>Ottenhoff, Tom H M</creator><creator>Heidt, Peter J</creator><creator>Gilbert, Sarah C</creator><creator>Gicquel, Brigitte</creator><creator>Hill, Adrian V S</creator><creator>Martin, Carlos</creator><creator>McShane, Helen</creator><creator>Thomas, Alan W</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7T7</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090415</creationdate><title>MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques</title><author>Verreck, Frank A W ; Vervenne, Richard A W ; Kondova, Ivanela ; van Kralingen, Klaas W ; Remarque, Edmond J ; Braskamp, Gerco ; van der Werff, Nicole M ; Kersbergen, Ariena ; Ottenhoff, Tom H M ; Heidt, Peter J ; Gilbert, Sarah C ; Gicquel, Brigitte ; Hill, Adrian V S ; Martin, Carlos ; McShane, Helen ; Thomas, Alan W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c721t-5dea70e2d826fa38ed6d91d3c4900717bd3ac53bc4ce5f7514c07491356e64423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acyltransferases - 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blood</topic><topic>Interferon-gamma - secretion</topic><topic>Lung - diagnostic imaging</topic><topic>Lung - pathology</topic><topic>Lungs</topic><topic>Lymphocytes</topic><topic>Macaca fascicularis</topic><topic>Macaca mulatta</topic><topic>Male</topic><topic>Monkeys</topic><topic>Monkeys & apes</topic><topic>Mycobacterium bovis</topic><topic>Mycobacterium bovis - immunology</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Parasitology</topic><topic>Phylogeny</topic><topic>Radiography</topic><topic>Sulfur dioxide</topic><topic>Treatment Outcome</topic><topic>Tuberculosis</topic><topic>Tuberculosis - immunology</topic><topic>Tuberculosis - microbiology</topic><topic>Tuberculosis - prevention & control</topic><topic>Tuberculosis vaccines</topic><topic>Tuberculosis Vaccines - immunology</topic><topic>Vaccination</topic><topic>Vaccine efficacy</topic><topic>Vaccines</topic><topic>Vaccines, Attenuated - immunology</topic><topic>Vaccines, DNA - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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 China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verreck, Frank A W</au><au>Vervenne, Richard A W</au><au>Kondova, Ivanela</au><au>van Kralingen, Klaas W</au><au>Remarque, Edmond J</au><au>Braskamp, Gerco</au><au>van der Werff, Nicole M</au><au>Kersbergen, Ariena</au><au>Ottenhoff, Tom H M</au><au>Heidt, Peter J</au><au>Gilbert, Sarah C</au><au>Gicquel, Brigitte</au><au>Hill, Adrian V S</au><au>Martin, Carlos</au><au>McShane, Helen</au><au>Thomas, Alan W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-04-15</date><risdate>2009</risdate><volume>4</volume><issue>4</issue><spage>e5264</spage><epage>e5264</epage><pages>e5264-e5264</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection.
Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A), and attenuated M. tuberculosis with a disrupted phoP gene (SO2) as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG) and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht) as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60).
Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19367339</pmid><doi>10.1371/journal.pone.0005264</doi><tpages>e5264</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-04, Vol.4 (4), p.e5264-e5264 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1290670691 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acyltransferases - immunology Animal sciences Animals Antigens Antigens, Bacterial - immunology Attenuation Bacillus Calmette-Guerin vaccine Bacteria Bacterial Proteins - genetics BCG BCG Vaccine - immunology Biomarkers - blood Biosynthesis Body weight Body weight loss C-reactive protein Clinical trials Colony Count, Microbial Disease Effectiveness Genomes Health aspects Identification methods Immunogenicity Immunology Immunology/Immunity to Infections Infections Infectious Diseases Infectious Diseases/Bacterial Infections Infectious Diseases/Respiratory Infections Inflammation Inflammation - blood Interferon-gamma - secretion Lung - diagnostic imaging Lung - pathology Lungs Lymphocytes Macaca fascicularis Macaca mulatta Male Monkeys Monkeys & apes Mycobacterium bovis Mycobacterium bovis - immunology Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Parasitology Phylogeny Radiography Sulfur dioxide Treatment Outcome Tuberculosis Tuberculosis - immunology Tuberculosis - microbiology Tuberculosis - prevention & control Tuberculosis vaccines Tuberculosis Vaccines - immunology Vaccination Vaccine efficacy Vaccines Vaccines, Attenuated - immunology Vaccines, DNA - immunology Vaccinia virus Vaccinia virus - immunology Viruses Weight reduction Zoology γ-Interferon |
| title | MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques |
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