Expression library immunization confers partial protection against Chlamydia muridarum genital infection
Abstract Protective sequences of Chlamydia muridarum were identified as potential vaccine candidates by screening a genomic DNA expression library and assessing the immune responses of mice immunized with individual library clones following vaginal challenge with live Chlamydia . Groups of female BA...
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| Veröffentlicht in: | Vaccine 2007-03, Vol.25 (14), p.2643-2655 |
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| creator | McNeilly, Celia L Beagley, Kenneth W Moore, Robert J Haring, Volker Timms, Peter Hafner, Louise M |
| description | Abstract Protective sequences of Chlamydia muridarum were identified as potential vaccine candidates by screening a genomic DNA expression library and assessing the immune responses of mice immunized with individual library clones following vaginal challenge with live Chlamydia . Groups of female BALB/c mice were immunized intra-abdominally by gene gun delivery of DNA three times at three-weekly intervals with individual library clones expressing chlamydial protein fragments and humoral and cell-mediated immune responses were evaluated. Chlamydia -specific cytokines including tumour necrosis factor-α (TNF-α) interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-12 (IL-12) and interferon-γ (IFN-γ) were detected in mice immunized either with selected DNA clones in spleen cells (0.2–135.2 pg/mL) or lymph nodes (0.15–84.9 pg/mL). The most protective antigen identified was TC0512, a putative outer membrane protein (OMP). Immunization of mice with this clone elicited T-helper type-1 (Th-1) and T-helper type-2 (Th-2) cytokines as well as and IgG1 and IgG2a in sera of these animals. Ten days after the last immunization, animals were challenged intra-vaginally with 5 × 104 inclusion-forming units (IFUs) of C. muridarum . At 9 days following challenge TC0512 showed a 73% reduction in the number of recoverable Chlamydia compared with vector only immunized controls. Six additional clones were identified that also conferred varying degrees of protection against live chlamydial challenge. Significant protection against the initial stages of infection was shown by two DNA clones (encoding hypothetical proteins) and five clones showed enhanced clearance of chlamydial infection following DNA immunization and live chlamydial challenge. These results demonstrate that the C. muridarum genome can be screened for individual vaccine candidates by genetic immunization and that the screen produces novel and partially protective vaccine candidates. |
| doi_str_mv | 10.1016/j.vaccine.2006.12.019 |
| format | Article |
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Groups of female BALB/c mice were immunized intra-abdominally by gene gun delivery of DNA three times at three-weekly intervals with individual library clones expressing chlamydial protein fragments and humoral and cell-mediated immune responses were evaluated. Chlamydia -specific cytokines including tumour necrosis factor-α (TNF-α) interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-12 (IL-12) and interferon-γ (IFN-γ) were detected in mice immunized either with selected DNA clones in spleen cells (0.2–135.2 pg/mL) or lymph nodes (0.15–84.9 pg/mL). The most protective antigen identified was TC0512, a putative outer membrane protein (OMP). Immunization of mice with this clone elicited T-helper type-1 (Th-1) and T-helper type-2 (Th-2) cytokines as well as and IgG1 and IgG2a in sera of these animals. Ten days after the last immunization, animals were challenged intra-vaginally with 5 × 104 inclusion-forming units (IFUs) of C. muridarum . At 9 days following challenge TC0512 showed a 73% reduction in the number of recoverable Chlamydia compared with vector only immunized controls. Six additional clones were identified that also conferred varying degrees of protection against live chlamydial challenge. Significant protection against the initial stages of infection was shown by two DNA clones (encoding hypothetical proteins) and five clones showed enhanced clearance of chlamydial infection following DNA immunization and live chlamydial challenge. These results demonstrate that the C. muridarum genome can be screened for individual vaccine candidates by genetic immunization and that the screen produces novel and partially protective vaccine candidates.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2006.12.019</identifier><identifier>PMID: 17239501</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animals ; Antibodies, Bacterial - blood ; Applied microbiology ; Bacterial Vaccines - immunology ; Bacteriology ; Biolistics ; Biological and medical sciences ; Chlamydia ; Chlamydia Infections - prevention & control ; Chlamydia muridarum ; Chlamydia muridarum - immunology ; Expression library immunization ; Female ; Fundamental and applied biological sciences. Psychology ; Gene gun ; Gene Library ; Immunization ; Interleukin-10 - biosynthesis ; Interleukin-4 - biosynthesis ; Mice ; Mice, Inbred BALB C ; Microbiology ; Miscellaneous ; Sequence Analysis, DNA ; Tumor Necrosis Factor-alpha - biosynthesis ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Vaccines, DNA - immunology ; Vagina - microbiology ; Vaginal Diseases - prevention & control</subject><ispartof>Vaccine, 2007-03, Vol.25 (14), p.2643-2655</ispartof><rights>Elsevier Ltd</rights><rights>2007 Elsevier Ltd</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-fccbb0c390b83ada074e2bc4f94aa019d33bbec8b2b3849d0ee53022d311445b3</citedby><cites>FETCH-LOGICAL-c479t-fccbb0c390b83ada074e2bc4f94aa019d33bbec8b2b3849d0ee53022d311445b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X06013491$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18626446$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17239501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McNeilly, Celia L</creatorcontrib><creatorcontrib>Beagley, Kenneth W</creatorcontrib><creatorcontrib>Moore, Robert J</creatorcontrib><creatorcontrib>Haring, Volker</creatorcontrib><creatorcontrib>Timms, Peter</creatorcontrib><creatorcontrib>Hafner, Louise M</creatorcontrib><title>Expression library immunization confers partial protection against Chlamydia muridarum genital infection</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract Protective sequences of Chlamydia muridarum were identified as potential vaccine candidates by screening a genomic DNA expression library and assessing the immune responses of mice immunized with individual library clones following vaginal challenge with live Chlamydia . Groups of female BALB/c mice were immunized intra-abdominally by gene gun delivery of DNA three times at three-weekly intervals with individual library clones expressing chlamydial protein fragments and humoral and cell-mediated immune responses were evaluated. Chlamydia -specific cytokines including tumour necrosis factor-α (TNF-α) interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-12 (IL-12) and interferon-γ (IFN-γ) were detected in mice immunized either with selected DNA clones in spleen cells (0.2–135.2 pg/mL) or lymph nodes (0.15–84.9 pg/mL). The most protective antigen identified was TC0512, a putative outer membrane protein (OMP). Immunization of mice with this clone elicited T-helper type-1 (Th-1) and T-helper type-2 (Th-2) cytokines as well as and IgG1 and IgG2a in sera of these animals. Ten days after the last immunization, animals were challenged intra-vaginally with 5 × 104 inclusion-forming units (IFUs) of C. muridarum . At 9 days following challenge TC0512 showed a 73% reduction in the number of recoverable Chlamydia compared with vector only immunized controls. Six additional clones were identified that also conferred varying degrees of protection against live chlamydial challenge. Significant protection against the initial stages of infection was shown by two DNA clones (encoding hypothetical proteins) and five clones showed enhanced clearance of chlamydial infection following DNA immunization and live chlamydial challenge. These results demonstrate that the C. muridarum genome can be screened for individual vaccine candidates by genetic immunization and that the screen produces novel and partially protective vaccine candidates.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antibodies, Bacterial - blood</subject><subject>Applied microbiology</subject><subject>Bacterial Vaccines - immunology</subject><subject>Bacteriology</subject><subject>Biolistics</subject><subject>Biological and medical sciences</subject><subject>Chlamydia</subject><subject>Chlamydia Infections - prevention & control</subject><subject>Chlamydia muridarum</subject><subject>Chlamydia muridarum - immunology</subject><subject>Expression library immunization</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene gun</subject><subject>Gene Library</subject><subject>Immunization</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-4 - biosynthesis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Sequence Analysis, DNA</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Vaccines, DNA - immunology</subject><subject>Vagina - microbiology</subject><subject>Vaginal Diseases - prevention & control</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EotvCTwDlAreE8Ue-LiC0agGpEgdA4mbZzqSdJXEWO6lYfj1Od6VKXHqyZD_vzOt5h7FXHAoOvHq3K-6Mc-SxEABVwUUBvH3CNrypZS5K3jxlGxCVyhWHn2fsPMYdAJSSt8_ZGa-FbEvgG3Z7-WcfMEaafDaQDSYcMhrHxdNfM6-XbvI9hpjtTZjJDNk-TDO6-ydzY8jHOdveDmY8dGSycQnUmbCM2Q16mhNOSX1Pv2DPejNEfHk6L9iPq8vv28_59ddPX7Yfr3On6nbOe-esBSdbsI00nYFaobBO9a0yJv2wk9JadI0VVjaq7QCxlCBEJzlXqrTygr091k1Gfy8YZz1SdDgMxuO0RF2DaCpZ8kdBkUAllUpgeQRdmGIM2Ot9oDENSnPQaxZ6p09Z6DULzYVOTpPu9anBYkfsHlSn4SfgzQkw0ZmhD8Y7ig9cU6X8VJW4D0cO09zuCIOOjtA77Cik4epuoketvP-vghvIU2r6Cw8Yd9MSfApFcx2TQH9bF2fdG6iSTdVy-Q9I5sIL</recordid><startdate>20070330</startdate><enddate>20070330</enddate><creator>McNeilly, Celia L</creator><creator>Beagley, Kenneth W</creator><creator>Moore, Robert J</creator><creator>Haring, Volker</creator><creator>Timms, Peter</creator><creator>Hafner, Louise M</creator><general>Elsevier Ltd</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>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20070330</creationdate><title>Expression library immunization confers partial protection against Chlamydia muridarum genital infection</title><author>McNeilly, Celia L ; Beagley, Kenneth W ; Moore, Robert J ; Haring, Volker ; Timms, Peter ; Hafner, Louise M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-fccbb0c390b83ada074e2bc4f94aa019d33bbec8b2b3849d0ee53022d311445b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antibodies, Bacterial - blood</topic><topic>Applied microbiology</topic><topic>Bacterial Vaccines - immunology</topic><topic>Bacteriology</topic><topic>Biolistics</topic><topic>Biological and medical sciences</topic><topic>Chlamydia</topic><topic>Chlamydia Infections - prevention & control</topic><topic>Chlamydia muridarum</topic><topic>Chlamydia muridarum - immunology</topic><topic>Expression library immunization</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene gun</topic><topic>Gene Library</topic><topic>Immunization</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-4 - biosynthesis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Sequence Analysis, DNA</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Vaccines</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</topic><topic>Vaccines, DNA - immunology</topic><topic>Vagina - microbiology</topic><topic>Vaginal Diseases - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McNeilly, Celia L</creatorcontrib><creatorcontrib>Beagley, Kenneth W</creatorcontrib><creatorcontrib>Moore, Robert J</creatorcontrib><creatorcontrib>Haring, Volker</creatorcontrib><creatorcontrib>Timms, Peter</creatorcontrib><creatorcontrib>Hafner, Louise M</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>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McNeilly, Celia L</au><au>Beagley, Kenneth W</au><au>Moore, Robert J</au><au>Haring, Volker</au><au>Timms, Peter</au><au>Hafner, Louise M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression library immunization confers partial protection against Chlamydia muridarum genital infection</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2007-03-30</date><risdate>2007</risdate><volume>25</volume><issue>14</issue><spage>2643</spage><epage>2655</epage><pages>2643-2655</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>Abstract Protective sequences of Chlamydia muridarum were identified as potential vaccine candidates by screening a genomic DNA expression library and assessing the immune responses of mice immunized with individual library clones following vaginal challenge with live Chlamydia . Groups of female BALB/c mice were immunized intra-abdominally by gene gun delivery of DNA three times at three-weekly intervals with individual library clones expressing chlamydial protein fragments and humoral and cell-mediated immune responses were evaluated. Chlamydia -specific cytokines including tumour necrosis factor-α (TNF-α) interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-12 (IL-12) and interferon-γ (IFN-γ) were detected in mice immunized either with selected DNA clones in spleen cells (0.2–135.2 pg/mL) or lymph nodes (0.15–84.9 pg/mL). The most protective antigen identified was TC0512, a putative outer membrane protein (OMP). Immunization of mice with this clone elicited T-helper type-1 (Th-1) and T-helper type-2 (Th-2) cytokines as well as and IgG1 and IgG2a in sera of these animals. Ten days after the last immunization, animals were challenged intra-vaginally with 5 × 104 inclusion-forming units (IFUs) of C. muridarum . At 9 days following challenge TC0512 showed a 73% reduction in the number of recoverable Chlamydia compared with vector only immunized controls. Six additional clones were identified that also conferred varying degrees of protection against live chlamydial challenge. Significant protection against the initial stages of infection was shown by two DNA clones (encoding hypothetical proteins) and five clones showed enhanced clearance of chlamydial infection following DNA immunization and live chlamydial challenge. These results demonstrate that the C. muridarum genome can be screened for individual vaccine candidates by genetic immunization and that the screen produces novel and partially protective vaccine candidates.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17239501</pmid><doi>10.1016/j.vaccine.2006.12.019</doi><tpages>13</tpages></addata></record> |
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| subjects | Allergy and Immunology Animals Antibodies, Bacterial - blood Applied microbiology Bacterial Vaccines - immunology Bacteriology Biolistics Biological and medical sciences Chlamydia Chlamydia Infections - prevention & control Chlamydia muridarum Chlamydia muridarum - immunology Expression library immunization Female Fundamental and applied biological sciences. Psychology Gene gun Gene Library Immunization Interleukin-10 - biosynthesis Interleukin-4 - biosynthesis Mice Mice, Inbred BALB C Microbiology Miscellaneous Sequence Analysis, DNA Tumor Necrosis Factor-alpha - biosynthesis Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Vaccines, DNA - immunology Vagina - microbiology Vaginal Diseases - prevention & control |
| title | Expression library immunization confers partial protection against Chlamydia muridarum genital infection |
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