Protective Immunity Against Tuberculosis Induced by Vaccination with Major Extracellular Proteins of Mycobacterium tuberculosis
Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major se...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1995-02, Vol.92 (5), p.1530-1534 |
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description | Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules. |
doi_str_mv | 10.1073/pnas.92.5.1530 |
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A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.92.5.1530</identifier><identifier>PMID: 7878014</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Animals ; Antigens, Bacterial - chemistry ; Bacteria ; Bacterial Proteins - chemistry ; Bacterial Proteins - immunology ; Bacterial Vaccines - immunology ; Body Weight ; Cellular biology ; Extracellular Space ; Guinea Pigs ; Hypersensitivity, Delayed ; Immunity ; Immunity (Disease) ; Immunization ; Lung - pathology ; Lungs ; Male ; Molecular Sequence Data ; Molecular Weight ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Pathogens ; Proteins ; Pulmonary tuberculosis ; Splenic tuberculosis ; Tuberculosis ; Tuberculosis vaccine ; Tuberculosis, Pulmonary - pathology ; Tuberculosis, Pulmonary - prevention & control ; Vaccines</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1995-02, Vol.92 (5), p.1530-1534</ispartof><rights>Copyright 1995 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 28, 1995</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-75ac302c7243d9466be9299f4e33adef2ccfef8f6736114b9c5c7b6709d73a8a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/92/5.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2366816$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2366816$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27906,27907,53773,53775,57999,58232</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7878014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horwitz, Marcus A.</creatorcontrib><creatorcontrib>Lee, Byong-Wha Esther</creatorcontrib><creatorcontrib>Dillon, Barbara Jane</creatorcontrib><creatorcontrib>Harth, Gunter</creatorcontrib><title>Protective Immunity Against Tuberculosis Induced by Vaccination with Major Extracellular Proteins of Mycobacterium tuberculosis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antigens, Bacterial - chemistry</subject><subject>Bacteria</subject><subject>Bacterial Proteins - chemistry</subject><subject>Bacterial Proteins - immunology</subject><subject>Bacterial Vaccines - immunology</subject><subject>Body Weight</subject><subject>Cellular biology</subject><subject>Extracellular Space</subject><subject>Guinea Pigs</subject><subject>Hypersensitivity, Delayed</subject><subject>Immunity</subject><subject>Immunity (Disease)</subject><subject>Immunization</subject><subject>Lung - pathology</subject><subject>Lungs</subject><subject>Male</subject><subject>Molecular Sequence Data</subject><subject>Molecular Weight</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Pathogens</subject><subject>Proteins</subject><subject>Pulmonary tuberculosis</subject><subject>Splenic tuberculosis</subject><subject>Tuberculosis</subject><subject>Tuberculosis vaccine</subject><subject>Tuberculosis, Pulmonary - pathology</subject><subject>Tuberculosis, Pulmonary - prevention & control</subject><subject>Vaccines</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1rFDEAxQdR6lq9elIIPXjbMZ-TCXgppepCix6q15DJZNosM8maj9o9-a-bcddlFUEI5PB-7_GSV1UvEawR5OTtxqlYC1yzGjECH1ULBAVaNlTAx9UCQsyXLcX0afUsxjWEULAWnlQnvOUtRHRR_fgcfDI62XsDVtOUnU1bcH6rrIsJ3OTOBJ1HH20EK9dnbXrQbcFXpbV1KlnvwHeb7sC1WvsALh9SUNqMYx5VAL-CSwzwA7jeat8pnUyweQLpKPZ59WRQYzQv9vdp9eX95c3Fx-XVpw-ri_OrpWaIpSVnShOINceU9II2TWcEFmKghhDVmwFrPZihHRpOGoRoJzTTvGs4FD0nqlXktHq3y93kbjK9Nq50HeUm2EmFrfTKyj8VZ-_krb-XFDNGiv3N3h78t2xikpON81OVMz5HyTligiLxXxCVTuWgAp79Ba59Dq78gcRFLktRXqB6B-ngYwxmOBRGUM7zy3l-KbBkcp6_GF4fP_OA7_c-qjf7fqsHvxzyOCbzkI6C_gkW_dVOX8fkwwHApGla1JCfzFnQkw</recordid><startdate>19950228</startdate><enddate>19950228</enddate><creator>Horwitz, Marcus A.</creator><creator>Lee, Byong-Wha Esther</creator><creator>Dillon, Barbara Jane</creator><creator>Harth, Gunter</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19950228</creationdate><title>Protective Immunity Against Tuberculosis Induced by Vaccination with Major Extracellular Proteins of Mycobacterium tuberculosis</title><author>Horwitz, Marcus A. ; Lee, Byong-Wha Esther ; Dillon, Barbara Jane ; Harth, Gunter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-75ac302c7243d9466be9299f4e33adef2ccfef8f6736114b9c5c7b6709d73a8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antigens, Bacterial - chemistry</topic><topic>Bacteria</topic><topic>Bacterial Proteins - chemistry</topic><topic>Bacterial Proteins - immunology</topic><topic>Bacterial Vaccines - immunology</topic><topic>Body Weight</topic><topic>Cellular biology</topic><topic>Extracellular Space</topic><topic>Guinea Pigs</topic><topic>Hypersensitivity, Delayed</topic><topic>Immunity</topic><topic>Immunity (Disease)</topic><topic>Immunization</topic><topic>Lung - pathology</topic><topic>Lungs</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Molecular Weight</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Pathogens</topic><topic>Proteins</topic><topic>Pulmonary tuberculosis</topic><topic>Splenic tuberculosis</topic><topic>Tuberculosis</topic><topic>Tuberculosis vaccine</topic><topic>Tuberculosis, Pulmonary - pathology</topic><topic>Tuberculosis, Pulmonary - prevention & control</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horwitz, Marcus A.</creatorcontrib><creatorcontrib>Lee, Byong-Wha Esther</creatorcontrib><creatorcontrib>Dillon, Barbara Jane</creatorcontrib><creatorcontrib>Harth, Gunter</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horwitz, Marcus A.</au><au>Lee, Byong-Wha Esther</au><au>Dillon, Barbara Jane</au><au>Harth, Gunter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective Immunity Against Tuberculosis Induced by Vaccination with Major Extracellular Proteins of Mycobacterium tuberculosis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1995-02-28</date><risdate>1995</risdate><volume>92</volume><issue>5</issue><spage>1530</spage><epage>1534</epage><pages>1530-1534</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. 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subjects | Amino Acid Sequence Animals Antigens, Bacterial - chemistry Bacteria Bacterial Proteins - chemistry Bacterial Proteins - immunology Bacterial Vaccines - immunology Body Weight Cellular biology Extracellular Space Guinea Pigs Hypersensitivity, Delayed Immunity Immunity (Disease) Immunization Lung - pathology Lungs Male Molecular Sequence Data Molecular Weight Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Pathogens Proteins Pulmonary tuberculosis Splenic tuberculosis Tuberculosis Tuberculosis vaccine Tuberculosis, Pulmonary - pathology Tuberculosis, Pulmonary - prevention & control Vaccines |
title | Protective Immunity Against Tuberculosis Induced by Vaccination with Major Extracellular Proteins of Mycobacterium tuberculosis |
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