Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1
Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elic...
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Veröffentlicht in: | Research in microbiology 1990-09, Vol.141 (7-8), p.907-912 |
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description | Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials. |
doi_str_mv | 10.1016/0923-2508(90)90129-E |
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No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.</description><identifier>ISSN: 0923-2508</identifier><identifier>EISSN: 1769-7123</identifier><identifier>DOI: 10.1016/0923-2508(90)90129-E</identifier><identifier>PMID: 2101481</identifier><language>eng</language><publisher>Paris: Elsevier Masson SAS</publisher><subject>Animals ; Bacterial Vaccines - genetics ; Bacterial Vaccines - isolation & purification ; Bacteriology ; Biological and medical sciences ; Fundamental and applied biological sciences. Psychology ; Humans ; Macaca ; Microbiology ; Mutation ; Shigella dysenteriae - genetics ; Shigella dysenteriae - immunology ; Shigella flexneri - genetics ; Shigella flexneri - immunology ; Shigella, Vaccine, Shigellosis ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies ; Vaccines, Attenuated - genetics ; Vaccines, Attenuated - isolation & purification ; Vaccines, Synthetic - genetics ; Vaccines, Synthetic - isolation & purification ; Virulence - genetics ; Virulence, Mutations</subject><ispartof>Research in microbiology, 1990-09, Vol.141 (7-8), p.907-912</ispartof><rights>1990</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-d8eb37271364df230bcc1d7a21003a292cb4cab0ed3ea52a6124e4c65bddef653</citedby><cites>FETCH-LOGICAL-c433t-d8eb37271364df230bcc1d7a21003a292cb4cab0ed3ea52a6124e4c65bddef653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0923-2508(90)90129-E$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,780,784,789,790,3550,23930,23931,25140,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19436170$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2101481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fontaine, A.</creatorcontrib><creatorcontrib>Arondel, J.</creatorcontrib><creatorcontrib>Sansonetti, P.J.</creatorcontrib><title>Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1</title><title>Research in microbiology</title><addtitle>Res Microbiol</addtitle><description>Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.</description><subject>Animals</subject><subject>Bacterial Vaccines - genetics</subject><subject>Bacterial Vaccines - isolation & purification</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Macaca</subject><subject>Microbiology</subject><subject>Mutation</subject><subject>Shigella dysenteriae - genetics</subject><subject>Shigella dysenteriae - immunology</subject><subject>Shigella flexneri - genetics</subject><subject>Shigella flexneri - immunology</subject><subject>Shigella, Vaccine, Shigellosis</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</subject><subject>Vaccines, Attenuated - genetics</subject><subject>Vaccines, Attenuated - isolation & purification</subject><subject>Vaccines, Synthetic - genetics</subject><subject>Vaccines, Synthetic - isolation & purification</subject><subject>Virulence - genetics</subject><subject>Virulence, Mutations</subject><issn>0923-2508</issn><issn>1769-7123</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF9r2zAUxcVoybJu36ADv7R0D-70z5b9Uigh2wqBPnR7FtfSdafhyKlkh-bbV05C-rYnoXPPORx-hFwyessoK7_TmoucF7S6qem3mjJe58sPZM5UWeeKcXFG5ifLR_Ipxn-UskIpOSMznhpkxebEL3ofhzCawfU-A28z3EI3wv7bt1nntpjBMKBPGtpsC8Y4j1nKgPNxsjz9dc_YdZC1Hb56DG5fc1LtLqIfkgyYsc_kvIUu4pfje0H-_Fj-XvzKV48_Hxb3q9xIIYbcVtgIxRUTpbQtF7QxhlkFaTYVwGtuGmmgoWgFQsGhZFyiNGXRWIttWYgLcn3o3YT-ZcQ46LWLZtrjsR-jrqhQpeRVMsqD0YQ-xoCt3gS3hrDTjOoJs54Y6omhrqneY9bLFPt67B-bNdpT6Mg13a-Od4gGujaANy6-d9dSlEzR5Ls7-DDB2DoMOhqH3qB1Ac2gbe_-P-QNU96a5A</recordid><startdate>19900901</startdate><enddate>19900901</enddate><creator>Fontaine, A.</creator><creator>Arondel, J.</creator><creator>Sansonetti, P.J.</creator><general>Elsevier Masson SAS</general><general>Elsevier</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>19900901</creationdate><title>Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1</title><author>Fontaine, A. ; Arondel, J. ; Sansonetti, P.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-d8eb37271364df230bcc1d7a21003a292cb4cab0ed3ea52a6124e4c65bddef653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Bacterial Vaccines - genetics</topic><topic>Bacterial Vaccines - isolation & purification</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Macaca</topic><topic>Microbiology</topic><topic>Mutation</topic><topic>Shigella dysenteriae - genetics</topic><topic>Shigella dysenteriae - immunology</topic><topic>Shigella flexneri - genetics</topic><topic>Shigella flexneri - immunology</topic><topic>Shigella, Vaccine, Shigellosis</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</topic><topic>Vaccines, Attenuated - genetics</topic><topic>Vaccines, Attenuated - isolation & purification</topic><topic>Vaccines, Synthetic - genetics</topic><topic>Vaccines, Synthetic - isolation & purification</topic><topic>Virulence - genetics</topic><topic>Virulence, Mutations</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fontaine, A.</creatorcontrib><creatorcontrib>Arondel, J.</creatorcontrib><creatorcontrib>Sansonetti, P.J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Research in microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fontaine, A.</au><au>Arondel, J.</au><au>Sansonetti, P.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1</atitle><jtitle>Research in microbiology</jtitle><addtitle>Res Microbiol</addtitle><date>1990-09-01</date><risdate>1990</risdate><volume>141</volume><issue>7-8</issue><spage>907</spage><epage>912</epage><pages>907-912</pages><issn>0923-2508</issn><eissn>1769-7123</eissn><abstract>Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.</abstract><cop>Paris</cop><pub>Elsevier Masson SAS</pub><pmid>2101481</pmid><doi>10.1016/0923-2508(90)90129-E</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bacterial Vaccines - genetics Bacterial Vaccines - isolation & purification Bacteriology Biological and medical sciences Fundamental and applied biological sciences. Psychology Humans Macaca Microbiology Mutation Shigella dysenteriae - genetics Shigella dysenteriae - immunology Shigella flexneri - genetics Shigella flexneri - immunology Shigella, Vaccine, Shigellosis Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Vaccines, Attenuated - genetics Vaccines, Attenuated - isolation & purification Vaccines, Synthetic - genetics Vaccines, Synthetic - isolation & purification Virulence - genetics Virulence, Mutations |
title | Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1 |
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