Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs
Development of multigenic constructs expressing Mycobacterium tuberculosis ( Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fus...
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| Veröffentlicht in: | Microbes and infection 2008-05, Vol.10 (6), p.605-612 |
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| creator | Sali, Michela Clarizio, Sandra Pusceddu, Cinzia Zumbo, Antonella Pecorini, Giovanni Rocca, Stefano Zanetti, Stefania Delogu, Giovanni Fadda, Giovanni |
| description | Development of multigenic constructs expressing
Mycobacterium tuberculosis (
Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three
Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with
Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five
Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted
Mtb proteins. |
| doi_str_mv | 10.1016/j.micinf.2008.02.012 |
| format | Article |
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Mycobacterium tuberculosis (
Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three
Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with
Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five
Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted
Mtb proteins.</description><identifier>ISSN: 1286-4579</identifier><identifier>EISSN: 1769-714X</identifier><identifier>DOI: 10.1016/j.micinf.2008.02.012</identifier><identifier>PMID: 18468935</identifier><language>eng</language><publisher>Lausanne: Elsevier SAS</publisher><subject>Animals ; Antigens, Bacterial - genetics ; Antigens, Bacterial - immunology ; Bacterial diseases ; Bacteriology ; Biological and medical sciences ; DNA vaccines ; Fundamental and applied biological sciences. Psychology ; Human bacterial diseases ; Infectious diseases ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Microbiology ; Miscellaneous ; Mycobacterium ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Recombinant Fusion Proteins - immunology ; Tuberculosis ; Tuberculosis - prevention & control ; Tuberculosis and atypical mycobacterial infections ; Tuberculosis Vaccines ; Tumor Cells, Cultured ; Vaccines, DNA - genetics ; Vaccines, DNA - immunology ; Vaccines, Synthetic</subject><ispartof>Microbes and infection, 2008-05, Vol.10 (6), p.605-612</ispartof><rights>2008 Elsevier Masson SAS</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-4a1a440d5da0aa527747cee189df9b88d392f3d83eb167ddd1a6628c6f7f5c763</citedby><cites>FETCH-LOGICAL-c467t-4a1a440d5da0aa527747cee189df9b88d392f3d83eb167ddd1a6628c6f7f5c763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.micinf.2008.02.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20412137$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18468935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sali, Michela</creatorcontrib><creatorcontrib>Clarizio, Sandra</creatorcontrib><creatorcontrib>Pusceddu, Cinzia</creatorcontrib><creatorcontrib>Zumbo, Antonella</creatorcontrib><creatorcontrib>Pecorini, Giovanni</creatorcontrib><creatorcontrib>Rocca, Stefano</creatorcontrib><creatorcontrib>Zanetti, Stefania</creatorcontrib><creatorcontrib>Delogu, Giovanni</creatorcontrib><creatorcontrib>Fadda, Giovanni</creatorcontrib><title>Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs</title><title>Microbes and infection</title><addtitle>Microbes Infect</addtitle><description>Development of multigenic constructs expressing
Mycobacterium tuberculosis (
Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three
Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with
Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five
Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted
Mtb proteins.</description><subject>Animals</subject><subject>Antigens, Bacterial - genetics</subject><subject>Antigens, Bacterial - immunology</subject><subject>Bacterial diseases</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>DNA vaccines</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Human bacterial diseases</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Mycobacterium</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Tuberculosis</subject><subject>Tuberculosis - prevention & control</subject><subject>Tuberculosis and atypical mycobacterial infections</subject><subject>Tuberculosis Vaccines</subject><subject>Tumor Cells, Cultured</subject><subject>Vaccines, DNA - genetics</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccines, Synthetic</subject><issn>1286-4579</issn><issn>1769-714X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2KFDEUhYMozo--gUg2uqsySaWS1EYYZsZxYHA2I7gLqeRG01SlxiTV0G_js_hkpulGd87qXrjfOVzOQegNJS0lVHzYtHOwIfqWEaJawlpC2TN0SqUYGkn5t-d1Z0o0vJfDCTrLeUMI7aXgL9EJVVyooetPEVxvzbSaEpaIF4_LD8AmltCUdYRk12nJIWNjS9iGssPfIUIyBRwed9gF7yFBLHhepxL2t9-_rr5c4K2x9THAdom5pNWW_Aq98GbK8Po4z9HXT9cPl5-bu_ub28uLu8ZyIUvDDTWcE9c7Q4zpmZRcWgCqBueHUSnXDcx3TnUwUiGdc9QIwZQVXvreStGdo_cH38e0_FwhFz2HbGGaTIRlzVpSQQcu-ZMgHWSNTagK8gNo05JzAq8fU5hN2mlK9L4HvdGHHvS-B02Yrj1U2duj_zrO4P6JjsFX4N0RMNmayScTbch_OUY4ZbSTlft44KDGtg2QdLYBogUXEtii3RL-_8kfgMeq3A</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Sali, Michela</creator><creator>Clarizio, Sandra</creator><creator>Pusceddu, Cinzia</creator><creator>Zumbo, Antonella</creator><creator>Pecorini, Giovanni</creator><creator>Rocca, Stefano</creator><creator>Zanetti, Stefania</creator><creator>Delogu, Giovanni</creator><creator>Fadda, Giovanni</creator><general>Elsevier 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>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20080501</creationdate><title>Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs</title><author>Sali, Michela ; Clarizio, Sandra ; Pusceddu, Cinzia ; Zumbo, Antonella ; Pecorini, Giovanni ; Rocca, Stefano ; Zanetti, Stefania ; Delogu, Giovanni ; Fadda, Giovanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-4a1a440d5da0aa527747cee189df9b88d392f3d83eb167ddd1a6628c6f7f5c763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antigens, Bacterial - genetics</topic><topic>Antigens, Bacterial - immunology</topic><topic>Bacterial diseases</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>DNA vaccines</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Human bacterial diseases</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Mycobacterium</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Tuberculosis</topic><topic>Tuberculosis - prevention & control</topic><topic>Tuberculosis and atypical mycobacterial infections</topic><topic>Tuberculosis Vaccines</topic><topic>Tumor Cells, Cultured</topic><topic>Vaccines, DNA - genetics</topic><topic>Vaccines, DNA - immunology</topic><topic>Vaccines, Synthetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sali, Michela</creatorcontrib><creatorcontrib>Clarizio, Sandra</creatorcontrib><creatorcontrib>Pusceddu, Cinzia</creatorcontrib><creatorcontrib>Zumbo, Antonella</creatorcontrib><creatorcontrib>Pecorini, Giovanni</creatorcontrib><creatorcontrib>Rocca, Stefano</creatorcontrib><creatorcontrib>Zanetti, Stefania</creatorcontrib><creatorcontrib>Delogu, Giovanni</creatorcontrib><creatorcontrib>Fadda, Giovanni</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids 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>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Microbes and infection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sali, Michela</au><au>Clarizio, Sandra</au><au>Pusceddu, Cinzia</au><au>Zumbo, Antonella</au><au>Pecorini, Giovanni</au><au>Rocca, Stefano</au><au>Zanetti, Stefania</au><au>Delogu, Giovanni</au><au>Fadda, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs</atitle><jtitle>Microbes and infection</jtitle><addtitle>Microbes Infect</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>10</volume><issue>6</issue><spage>605</spage><epage>612</epage><pages>605-612</pages><issn>1286-4579</issn><eissn>1769-714X</eissn><abstract>Development of multigenic constructs expressing
Mycobacterium tuberculosis (
Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three
Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with
Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five
Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted
Mtb proteins.</abstract><cop>Lausanne</cop><cop>Amsterdam</cop><cop>Paris</cop><pub>Elsevier SAS</pub><pmid>18468935</pmid><doi>10.1016/j.micinf.2008.02.012</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1286-4579 |
| ispartof | Microbes and infection, 2008-05, Vol.10 (6), p.605-612 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Antigens, Bacterial - genetics Antigens, Bacterial - immunology Bacterial diseases Bacteriology Biological and medical sciences DNA vaccines Fundamental and applied biological sciences. Psychology Human bacterial diseases Infectious diseases Medical sciences Mice Mice, Inbred C57BL Microbiology Miscellaneous Mycobacterium Mycobacterium tuberculosis Mycobacterium tuberculosis - immunology Recombinant Fusion Proteins - immunology Tuberculosis Tuberculosis - prevention & control Tuberculosis and atypical mycobacterial infections Tuberculosis Vaccines Tumor Cells, Cultured Vaccines, DNA - genetics Vaccines, DNA - immunology Vaccines, Synthetic |
| title | Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs |
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