Monoclonal antibodies targeting different cell wall antigens of group B streptococcus mediate protection in both Fc-dependent and independent manner
Abstract Group B streptococcus remains an important neonatal pathogen in spite of widely adopted intrapartum antibiotic administration; therefore immune prophylaxis for GBS infections is highly warranted. In passive immunization and lethal challenge studies with multiple GBS strains, we characterize...
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| Veröffentlicht in: | Vaccine 2011-05, Vol.29 (24), p.4116-4124 |
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| creator | Senn, Beatrice M Visram, Zehra Meinke, Andreas L Neubauer, Christina Gelbmann, Dieter Sinzinger, Jan Hanner, Markus Lundberg, Urban Boisvert, Heike Reinscheid, Dieter von Gabain, Alexander Nagy, Eszter |
| description | Abstract Group B streptococcus remains an important neonatal pathogen in spite of widely adopted intrapartum antibiotic administration; therefore immune prophylaxis for GBS infections is highly warranted. In passive immunization and lethal challenge studies with multiple GBS strains, we characterized the protective effect of rabbit polyclonal and murine monoclonal antibodies specific for four multi-functional cell wall anchored proteins, FbsA, BibA, PilA and PilB. Single specificity rabbit sera or mAbs induced high level, but strain dependent protection, while their combinations resulted in superior and broad efficacy against all GBS strains tested. Polyclonal and monoclonal antibodies specific for the pilus proteins exerted very potent opsonophagocytic killing activity in vitro and required the Fc domain for protection in vivo . In contrast, FbsA and BibA specific antibodies failed to show OPK activity, but their Fab fragments fully protected animals, suggesting that blocking the function of these proteins was the major mode of action. These data are supportive for developing immune prophylaxis with human mAbs for prematurely born neonates who receive low levels of antibodies by maternofetal transport and are characterized by not fully developed phagocytic and complement activity. |
| doi_str_mv | 10.1016/j.vaccine.2011.03.100 |
| format | Article |
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In passive immunization and lethal challenge studies with multiple GBS strains, we characterized the protective effect of rabbit polyclonal and murine monoclonal antibodies specific for four multi-functional cell wall anchored proteins, FbsA, BibA, PilA and PilB. Single specificity rabbit sera or mAbs induced high level, but strain dependent protection, while their combinations resulted in superior and broad efficacy against all GBS strains tested. Polyclonal and monoclonal antibodies specific for the pilus proteins exerted very potent opsonophagocytic killing activity in vitro and required the Fc domain for protection in vivo . In contrast, FbsA and BibA specific antibodies failed to show OPK activity, but their Fab fragments fully protected animals, suggesting that blocking the function of these proteins was the major mode of action. These data are supportive for developing immune prophylaxis with human mAbs for prematurely born neonates who receive low levels of antibodies by maternofetal transport and are characterized by not fully developed phagocytic and complement activity.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2011.03.100</identifier><identifier>PMID: 21496467</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animals ; Anti-infective monoclonal antibody ; Antibiotics ; Antibodies, Bacterial - administration & dosage ; Antibodies, Bacterial - immunology ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - immunology ; antigens ; Antigens, Bacterial - immunology ; Applied microbiology ; Bacteriology ; Biological and medical sciences ; Cell Wall - immunology ; cell walls ; complement ; Disease ; disease control ; Disease Models, Animal ; Female ; fimbriae ; Fundamental and applied biological sciences. Psychology ; Group B streptococcus ; humans ; Immune prophylaxis ; Immunization ; Immunization, Passive - methods ; Infections ; mechanism of action ; Mice ; Microbiology ; Miscellaneous ; Mode of action ; monoclonal antibodies ; Mortality ; Neonates ; Older people ; Pathogenesis ; pathogens ; Phagocytosis ; Prophylaxis ; Protected animals ; Protective antigens ; protective effect ; Proteins ; Rabbits ; Streptococcal Infections - prevention & control ; Streptococcus ; Streptococcus agalactiae ; Streptococcus agalactiae - immunology ; Studies ; Survival Analysis ; Treatment Outcome ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Womens health</subject><ispartof>Vaccine, 2011-05, Vol.29 (24), p.4116-4124</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited May 31, 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-52af1f63d5fe5c641d42303cf239cd479be7191472ba6676a08dc0a8482d02843</citedby><cites>FETCH-LOGICAL-c533t-52af1f63d5fe5c641d42303cf239cd479be7191472ba6676a08dc0a8482d02843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X11004932$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24234186$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21496467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Senn, Beatrice M</creatorcontrib><creatorcontrib>Visram, Zehra</creatorcontrib><creatorcontrib>Meinke, Andreas L</creatorcontrib><creatorcontrib>Neubauer, Christina</creatorcontrib><creatorcontrib>Gelbmann, Dieter</creatorcontrib><creatorcontrib>Sinzinger, Jan</creatorcontrib><creatorcontrib>Hanner, Markus</creatorcontrib><creatorcontrib>Lundberg, Urban</creatorcontrib><creatorcontrib>Boisvert, Heike</creatorcontrib><creatorcontrib>Reinscheid, Dieter</creatorcontrib><creatorcontrib>von Gabain, Alexander</creatorcontrib><creatorcontrib>Nagy, Eszter</creatorcontrib><title>Monoclonal antibodies targeting different cell wall antigens of group B streptococcus mediate protection in both Fc-dependent and independent manner</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract Group B streptococcus remains an important neonatal pathogen in spite of widely adopted intrapartum antibiotic administration; therefore immune prophylaxis for GBS infections is highly warranted. In passive immunization and lethal challenge studies with multiple GBS strains, we characterized the protective effect of rabbit polyclonal and murine monoclonal antibodies specific for four multi-functional cell wall anchored proteins, FbsA, BibA, PilA and PilB. Single specificity rabbit sera or mAbs induced high level, but strain dependent protection, while their combinations resulted in superior and broad efficacy against all GBS strains tested. Polyclonal and monoclonal antibodies specific for the pilus proteins exerted very potent opsonophagocytic killing activity in vitro and required the Fc domain for protection in vivo . In contrast, FbsA and BibA specific antibodies failed to show OPK activity, but their Fab fragments fully protected animals, suggesting that blocking the function of these proteins was the major mode of action. These data are supportive for developing immune prophylaxis with human mAbs for prematurely born neonates who receive low levels of antibodies by maternofetal transport and are characterized by not fully developed phagocytic and complement activity.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Anti-infective monoclonal antibody</subject><subject>Antibiotics</subject><subject>Antibodies, Bacterial - administration & dosage</subject><subject>Antibodies, Bacterial - immunology</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>antigens</subject><subject>Antigens, Bacterial - immunology</subject><subject>Applied microbiology</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Cell Wall - immunology</subject><subject>cell walls</subject><subject>complement</subject><subject>Disease</subject><subject>disease control</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>fimbriae</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Group B streptococcus</subject><subject>humans</subject><subject>Immune prophylaxis</subject><subject>Immunization</subject><subject>Immunization, Passive - methods</subject><subject>Infections</subject><subject>mechanism of action</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Mode of action</subject><subject>monoclonal antibodies</subject><subject>Mortality</subject><subject>Neonates</subject><subject>Older people</subject><subject>Pathogenesis</subject><subject>pathogens</subject><subject>Phagocytosis</subject><subject>Prophylaxis</subject><subject>Protected animals</subject><subject>Protective antigens</subject><subject>protective effect</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Streptococcal Infections - prevention & control</subject><subject>Streptococcus</subject><subject>Streptococcus agalactiae</subject><subject>Streptococcus agalactiae - immunology</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Womens health</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNks-KFDEQxhtR3HH1EdSAiKce86_T3RdFF1eFFQ_rgreQSarHjD3JmKRX9j18YKuZ0YG9KARCKr_6Uqmvquoxo0tGmXq5WV4ba32AJaeMLanAML1TLVjXipo3rLtbLShXspaMfj2pHuS8oZQ2gvX3qxPOZK-kahfVr08xRDvGYEZiQvGr6DxkUkxaQ_FhTZwfBkgQCrEwjuSnGffgGkImcSDrFKcdeUtySbAr0UZrp0y24LwpQHYpFrDFx0B8IKtYvpFzWzvYQXCzpgkOL47nrQkB0sPq3mDGDI8O-2l1df7uy9mH-uLz-49nby5q2whR6oabgQ1KuGaAxirJnOSCCjtw0Vsn234FLeuZbPnKKNUqQztnqelkxx3lnRSn1Yu9Lpb5Y4Jc9Nbn-ZsmQJyy7lrFpWLNf5CqE23T9wLJZ7fITZwStjdrpljXSyypRarZUzbFnBMMepf81qQbzaie_dUbffBXz_5qKjBMMe_JQX1aYY__Zv0xFIHnB8Bka8YhmWB9PnLYIck6hdzTPTeYqM06IXN1iS81lDLR40Li9Z4AdODaQ9LZeggWnU1oqXbR_7PYV7cU7OiDx7K-ww3kY1905prqy3lc52llmCx7wcVvNznlgg</recordid><startdate>20110531</startdate><enddate>20110531</enddate><creator>Senn, Beatrice M</creator><creator>Visram, Zehra</creator><creator>Meinke, Andreas L</creator><creator>Neubauer, Christina</creator><creator>Gelbmann, Dieter</creator><creator>Sinzinger, Jan</creator><creator>Hanner, Markus</creator><creator>Lundberg, Urban</creator><creator>Boisvert, Heike</creator><creator>Reinscheid, Dieter</creator><creator>von Gabain, Alexander</creator><creator>Nagy, Eszter</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>FBQ</scope><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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20110531</creationdate><title>Monoclonal antibodies targeting different cell wall antigens of group B streptococcus mediate protection in both Fc-dependent and independent manner</title><author>Senn, Beatrice M ; Visram, Zehra ; Meinke, Andreas L ; Neubauer, Christina ; Gelbmann, Dieter ; Sinzinger, Jan ; Hanner, Markus ; Lundberg, Urban ; Boisvert, Heike ; Reinscheid, Dieter ; von Gabain, Alexander ; Nagy, Eszter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-52af1f63d5fe5c641d42303cf239cd479be7191472ba6676a08dc0a8482d02843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Anti-infective monoclonal antibody</topic><topic>Antibiotics</topic><topic>Antibodies, Bacterial - administration & dosage</topic><topic>Antibodies, Bacterial - immunology</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>antigens</topic><topic>Antigens, Bacterial - immunology</topic><topic>Applied microbiology</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Cell Wall - immunology</topic><topic>cell walls</topic><topic>complement</topic><topic>Disease</topic><topic>disease control</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>fimbriae</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Group B streptococcus</topic><topic>humans</topic><topic>Immune prophylaxis</topic><topic>Immunization</topic><topic>Immunization, Passive - methods</topic><topic>Infections</topic><topic>mechanism of action</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Mode of action</topic><topic>monoclonal antibodies</topic><topic>Mortality</topic><topic>Neonates</topic><topic>Older people</topic><topic>Pathogenesis</topic><topic>pathogens</topic><topic>Phagocytosis</topic><topic>Prophylaxis</topic><topic>Protected animals</topic><topic>Protective antigens</topic><topic>protective effect</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Streptococcal Infections - prevention & control</topic><topic>Streptococcus</topic><topic>Streptococcus agalactiae</topic><topic>Streptococcus agalactiae - immunology</topic><topic>Studies</topic><topic>Survival Analysis</topic><topic>Treatment 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| ispartof | Vaccine, 2011-05, Vol.29 (24), p.4116-4124 |
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| subjects | Allergy and Immunology Animals Anti-infective monoclonal antibody Antibiotics Antibodies, Bacterial - administration & dosage Antibodies, Bacterial - immunology Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - immunology antigens Antigens, Bacterial - immunology Applied microbiology Bacteriology Biological and medical sciences Cell Wall - immunology cell walls complement Disease disease control Disease Models, Animal Female fimbriae Fundamental and applied biological sciences. Psychology Group B streptococcus humans Immune prophylaxis Immunization Immunization, Passive - methods Infections mechanism of action Mice Microbiology Miscellaneous Mode of action monoclonal antibodies Mortality Neonates Older people Pathogenesis pathogens Phagocytosis Prophylaxis Protected animals Protective antigens protective effect Proteins Rabbits Streptococcal Infections - prevention & control Streptococcus Streptococcus agalactiae Streptococcus agalactiae - immunology Studies Survival Analysis Treatment Outcome Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Womens health |
| title | Monoclonal antibodies targeting different cell wall antigens of group B streptococcus mediate protection in both Fc-dependent and independent manner |
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