A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Con...
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| Veröffentlicht in: | PloS one 2014-11, Vol.9 (11), p.e112848-e112848 |
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| creator | da Costa, Adeliane Castro Costa-Júnior, Abadio de Oliveira de Oliveira, Fábio Muniz Nogueira, Sarah Veloso Rosa, Joseane Damaceno Resende, Danilo Pires Kipnis, André Junqueira-Kipnis, Ana Paula |
| description | Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. |
| doi_str_mv | 10.1371/journal.pone.0112848 |
| format | Article |
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The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0112848</identifier><identifier>PMID: 25398087</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Analysis ; Animal models ; Animals ; Antigenic determinants ; Antigens ; Antigens, Bacterial - genetics ; Antigens, Bacterial - metabolism ; Antitubercular agents ; Bacillus Calmette-Guerin vaccine ; Bacteria ; Bacterial Load - immunology ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; BCG ; BCG Vaccine - immunology ; Biology and Life Sciences ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; Clinical trials ; Cytokines ; Cytokines - metabolism ; Disease ; Effector cells ; Epitopes ; Epitopes - immunology ; Female ; Fusion protein ; Helper cells ; Immune response ; Immune system ; Immunization ; Immunogenicity ; Infections ; Infectious diseases ; Lesions ; Lung - metabolism ; Lung - microbiology ; Lung - pathology ; Lungs ; Lymphocytes ; Lymphocytes T ; Macrophages ; Macrophages - cytology ; Macrophages - immunology ; Medical research ; Medicine and Health Sciences ; Mice ; Mice, Inbred BALB C ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Mycobacterium tuberculosis - metabolism ; Mycobacterium tuberculosis - pathogenicity ; Nitric oxide ; Nitric Oxide - metabolism ; Peritoneum ; Peritoneum - cytology ; Phagocytosis ; Proteins ; Public health ; Recombinant Fusion Proteins - biosynthesis ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - immunology ; Recombinant proteins ; Spleen ; Spleen - immunology ; Spleen - metabolism ; Th1 Cells - cytology ; Th1 Cells - immunology ; Th17 Cells - cytology ; Th17 Cells - immunology ; Tuberculosis ; Tuberculosis - immunology ; Tuberculosis - prevention & control ; Tuberculosis vaccines ; Vaccination ; Vaccines</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e112848-e112848</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Costa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (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>2014 Costa et al 2014 Costa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a76c60cb2d2f43c2fba05cf5d1d8352b66c852d0b0da815831f41f6fdf4327c93</citedby><cites>FETCH-LOGICAL-c692t-a76c60cb2d2f43c2fba05cf5d1d8352b66c852d0b0da815831f41f6fdf4327c93</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/PMC4232451/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232451/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25398087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chatterjee, Delphi</contributor><creatorcontrib>da Costa, Adeliane Castro</creatorcontrib><creatorcontrib>Costa-Júnior, Abadio de Oliveira</creatorcontrib><creatorcontrib>de Oliveira, Fábio Muniz</creatorcontrib><creatorcontrib>Nogueira, Sarah Veloso</creatorcontrib><creatorcontrib>Rosa, Joseane Damaceno</creatorcontrib><creatorcontrib>Resende, Danilo Pires</creatorcontrib><creatorcontrib>Kipnis, André</creatorcontrib><creatorcontrib>Junqueira-Kipnis, Ana Paula</creatorcontrib><title>A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.</description><subject>Adults</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigenic determinants</subject><subject>Antigens</subject><subject>Antigens, Bacterial - genetics</subject><subject>Antigens, Bacterial - metabolism</subject><subject>Antitubercular agents</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>Bacteria</subject><subject>Bacterial Load - immunology</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>BCG</subject><subject>BCG Vaccine - immunology</subject><subject>Biology and Life Sciences</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Disease</subject><subject>Effector cells</subject><subject>Epitopes</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Fusion protein</subject><subject>Helper cells</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Lesions</subject><subject>Lung - metabolism</subject><subject>Lung - microbiology</subject><subject>Lung - pathology</subject><subject>Lungs</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mycobacterium bovis</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Mycobacterium tuberculosis - metabolism</subject><subject>Mycobacterium tuberculosis - pathogenicity</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Peritoneum</subject><subject>Peritoneum - cytology</subject><subject>Phagocytosis</subject><subject>Proteins</subject><subject>Public health</subject><subject>Recombinant Fusion Proteins - biosynthesis</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Recombinant proteins</subject><subject>Spleen</subject><subject>Spleen - immunology</subject><subject>Spleen - metabolism</subject><subject>Th1 Cells - cytology</subject><subject>Th1 Cells - immunology</subject><subject>Th17 Cells - cytology</subject><subject>Th17 Cells - immunology</subject><subject>Tuberculosis</subject><subject>Tuberculosis - immunology</subject><subject>Tuberculosis - prevention & control</subject><subject>Tuberculosis 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new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis</title><author>da Costa, Adeliane Castro ; Costa-Júnior, Abadio de Oliveira ; de Oliveira, Fábio Muniz ; Nogueira, Sarah Veloso ; Rosa, Joseane Damaceno ; Resende, Danilo Pires ; Kipnis, André ; Junqueira-Kipnis, Ana Paula</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a76c60cb2d2f43c2fba05cf5d1d8352b66c852d0b0da815831f41f6fdf4327c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adults</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antigenic determinants</topic><topic>Antigens</topic><topic>Antigens, Bacterial - genetics</topic><topic>Antigens, Bacterial - metabolism</topic><topic>Antitubercular agents</topic><topic>Bacillus Calmette-Guerin vaccine</topic><topic>Bacteria</topic><topic>Bacterial Load 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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>ProQuest Biological Science Journals</collection><collection>ProQuest Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</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>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>da Costa, Adeliane Castro</au><au>Costa-Júnior, Abadio de Oliveira</au><au>de Oliveira, Fábio Muniz</au><au>Nogueira, Sarah Veloso</au><au>Rosa, Joseane Damaceno</au><au>Resende, Danilo Pires</au><au>Kipnis, André</au><au>Junqueira-Kipnis, Ana Paula</au><au>Chatterjee, Delphi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-14</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e112848</spage><epage>e112848</epage><pages>e112848-e112848</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25398087</pmid><doi>10.1371/journal.pone.0112848</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-11, Vol.9 (11), p.e112848-e112848 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1979937174 |
| source | PubMed (Medline); MEDLINE; Public Library of Science; DOAJ Directory of Open Access Journals; Free E-Journal (出版社公開部分のみ）; Free Full-Text Journals in Chemistry |
| subjects | Adults Analysis Animal models Animals Antigenic determinants Antigens Antigens, Bacterial - genetics Antigens, Bacterial - metabolism Antitubercular agents Bacillus Calmette-Guerin vaccine Bacteria Bacterial Load - immunology Bacterial Proteins - genetics Bacterial Proteins - metabolism BCG BCG Vaccine - immunology Biology and Life Sciences CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology Clinical trials Cytokines Cytokines - metabolism Disease Effector cells Epitopes Epitopes - immunology Female Fusion protein Helper cells Immune response Immune system Immunization Immunogenicity Infections Infectious diseases Lesions Lung - metabolism Lung - microbiology Lung - pathology Lungs Lymphocytes Lymphocytes T Macrophages Macrophages - cytology Macrophages - immunology Medical research Medicine and Health Sciences Mice Mice, Inbred BALB C Mycobacterium bovis Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Mycobacterium tuberculosis - metabolism Mycobacterium tuberculosis - pathogenicity Nitric oxide Nitric Oxide - metabolism Peritoneum Peritoneum - cytology Phagocytosis Proteins Public health Recombinant Fusion Proteins - biosynthesis Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Recombinant proteins Spleen Spleen - immunology Spleen - metabolism Th1 Cells - cytology Th1 Cells - immunology Th17 Cells - cytology Th17 Cells - immunology Tuberculosis Tuberculosis - immunology Tuberculosis - prevention & control Tuberculosis vaccines Vaccination Vaccines |
| title | A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis |
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