Immunization with a recombinant BibA surface protein confers immunity and protects mice against group B Streptococcus (GBS) vaginal colonization
•Recombinant GBS-V BibA induced local and systemic immune responses in immunized mice.•BibA-specific antibodies reduced GBS-V invasion and increased the opsonophagocytosis.•BibA immunization reduced vaginal colonization by GBS-V in mice.•Immunized mice were protected against lethal parenteral challe...
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Veröffentlicht in: | Vaccine 2020-07, Vol.38 (33), p.5286-5296 |
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creator | dos Santos, Nayara Fernanda Barros da Silva, Lukas Raposo Costa, Fagner James Martins Dantas de Mattos, Daniely Maranhão de Carvalho, Enéas Ferreira, Luís Carlos de Souza Ferreira, Rita de Cássia Café |
description | •Recombinant GBS-V BibA induced local and systemic immune responses in immunized mice.•BibA-specific antibodies reduced GBS-V invasion and increased the opsonophagocytosis.•BibA immunization reduced vaginal colonization by GBS-V in mice.•Immunized mice were protected against lethal parenteral challenge with GBS-V.•Passive immunity mediated by anti-BibA antibodies protected naïve mice from GBS-V colonization.
Streptococcus agalactiae or group B Streptococcus (GBS) is a Gram-positive bacterium divided into ten distinct serotypes that colonizes the vaginal and rectal tracts of approximately 30% of women worldwide. GBS is the leading cause of invasive infection in newborns, causing sepsis, pneumoniae and meningitis. The main strategy to prevent GSB infection in newborns includes the use of intrapartum antibiotic therapy, which does not prevent late-onset diseases and may select resistant bacterial strains. We still do not have a vaccine formulation specific for this pathogen approved for human use. Conserved surface proteins are potential antigens that could be targets for recognition by antibodies and activation of cell opsonization. We used a serotype V GBS (GBS-V)-derived recombinant surface protein, rBibA, and evaluated the potential protective role of the induced antigen-specific antibodies after parenteral or mucosal immunizations in C57BL/6 mice. In vitro and in vivo assays demonstrated that vaccine formulations containing BibA combined with different adjuvants induced serum IgG and/or secreted IgA antibodies, leading to enhanced opsonophagocytosis of GBS-V cells and reduced invasion of epithelial cells. One BibA-based vaccine formulation adjuvanted with a nontoxic derivative of the heat-labile toxin produced by enterotoxigenic Escherichia coli (ETEC) strains was capable of inducing protection against vaginal colonization and lethal parenteral challenge with GBS-V. Serum collected from vaccinated mice conferred passive protection against vaginal colonization in naïve mice challenged with GBS-V. Taken together, the present data demonstrate that the BibA protein is a promising antigen for development of a vaccine to protect against GBS infection. |
doi_str_mv | 10.1016/j.vaccine.2020.05.076 |
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Streptococcus agalactiae or group B Streptococcus (GBS) is a Gram-positive bacterium divided into ten distinct serotypes that colonizes the vaginal and rectal tracts of approximately 30% of women worldwide. GBS is the leading cause of invasive infection in newborns, causing sepsis, pneumoniae and meningitis. The main strategy to prevent GSB infection in newborns includes the use of intrapartum antibiotic therapy, which does not prevent late-onset diseases and may select resistant bacterial strains. We still do not have a vaccine formulation specific for this pathogen approved for human use. Conserved surface proteins are potential antigens that could be targets for recognition by antibodies and activation of cell opsonization. We used a serotype V GBS (GBS-V)-derived recombinant surface protein, rBibA, and evaluated the potential protective role of the induced antigen-specific antibodies after parenteral or mucosal immunizations in C57BL/6 mice. In vitro and in vivo assays demonstrated that vaccine formulations containing BibA combined with different adjuvants induced serum IgG and/or secreted IgA antibodies, leading to enhanced opsonophagocytosis of GBS-V cells and reduced invasion of epithelial cells. One BibA-based vaccine formulation adjuvanted with a nontoxic derivative of the heat-labile toxin produced by enterotoxigenic Escherichia coli (ETEC) strains was capable of inducing protection against vaginal colonization and lethal parenteral challenge with GBS-V. Serum collected from vaccinated mice conferred passive protection against vaginal colonization in naïve mice challenged with GBS-V. Taken together, the present data demonstrate that the BibA protein is a promising antigen for development of a vaccine to protect against GBS infection.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2020.05.076</identifier><identifier>PMID: 32571719</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adjuvants ; Animals ; Antibiotics ; Antibodies ; Antibodies, Bacterial ; Antigens ; Bacteria ; Bacterial infections ; Cell activation ; Chromatography ; Colonization ; Combined vaccines ; Disease ; E coli ; Epithelial cells ; Female ; Immunity (Disease) ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Infections ; Lymphocytes ; Membrane Proteins ; Meningitis ; Mice ; Mice, Inbred C57BL ; Mucosa ; Neonates ; Opsonization ; Opsonophagocytosis ; Pathogens ; Proteins ; Recombinant ; Rectum ; Sepsis ; Serotypes ; Strains (organisms) ; Streptococcal Infections - prevention & control ; Streptococcus ; Streptococcus agalactiae ; Streptococcus infections ; Target recognition ; Toxins ; Vaccine ; Vaccines ; Vagina ; Vaginal colonization</subject><ispartof>Vaccine, 2020-07, Vol.38 (33), p.5286-5296</ispartof><rights>2020 The Author(s)</rights><rights>Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><rights>2020. The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-f97f04e4a66a9de4e6f4cf87673fb17c0651fe60fc918b1e3f3b4629050be0003</citedby><cites>FETCH-LOGICAL-c440t-f97f04e4a66a9de4e6f4cf87673fb17c0651fe60fc918b1e3f3b4629050be0003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X20307313$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32571719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>dos Santos, Nayara Fernanda Barros</creatorcontrib><creatorcontrib>da Silva, Lukas Raposo</creatorcontrib><creatorcontrib>Costa, Fagner James Martins Dantas</creatorcontrib><creatorcontrib>de Mattos, Daniely Maranhão</creatorcontrib><creatorcontrib>de Carvalho, Enéas</creatorcontrib><creatorcontrib>Ferreira, Luís Carlos de Souza</creatorcontrib><creatorcontrib>Ferreira, Rita de Cássia Café</creatorcontrib><title>Immunization with a recombinant BibA surface protein confers immunity and protects mice against group B Streptococcus (GBS) vaginal colonization</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•Recombinant GBS-V BibA induced local and systemic immune responses in immunized mice.•BibA-specific antibodies reduced GBS-V invasion and increased the opsonophagocytosis.•BibA immunization reduced vaginal colonization by GBS-V in mice.•Immunized mice were protected against lethal parenteral challenge with GBS-V.•Passive immunity mediated by anti-BibA antibodies protected naïve mice from GBS-V colonization.
Streptococcus agalactiae or group B Streptococcus (GBS) is a Gram-positive bacterium divided into ten distinct serotypes that colonizes the vaginal and rectal tracts of approximately 30% of women worldwide. GBS is the leading cause of invasive infection in newborns, causing sepsis, pneumoniae and meningitis. The main strategy to prevent GSB infection in newborns includes the use of intrapartum antibiotic therapy, which does not prevent late-onset diseases and may select resistant bacterial strains. We still do not have a vaccine formulation specific for this pathogen approved for human use. Conserved surface proteins are potential antigens that could be targets for recognition by antibodies and activation of cell opsonization. We used a serotype V GBS (GBS-V)-derived recombinant surface protein, rBibA, and evaluated the potential protective role of the induced antigen-specific antibodies after parenteral or mucosal immunizations in C57BL/6 mice. In vitro and in vivo assays demonstrated that vaccine formulations containing BibA combined with different adjuvants induced serum IgG and/or secreted IgA antibodies, leading to enhanced opsonophagocytosis of GBS-V cells and reduced invasion of epithelial cells. One BibA-based vaccine formulation adjuvanted with a nontoxic derivative of the heat-labile toxin produced by enterotoxigenic Escherichia coli (ETEC) strains was capable of inducing protection against vaginal colonization and lethal parenteral challenge with GBS-V. Serum collected from vaccinated mice conferred passive protection against vaginal colonization in naïve mice challenged with GBS-V. Taken together, the present data demonstrate that the BibA protein is a promising antigen for development of a vaccine to protect against GBS infection.</description><subject>Adjuvants</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Antibodies</subject><subject>Antibodies, Bacterial</subject><subject>Antigens</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>Cell activation</subject><subject>Chromatography</subject><subject>Colonization</subject><subject>Combined vaccines</subject><subject>Disease</subject><subject>E coli</subject><subject>Epithelial cells</subject><subject>Female</subject><subject>Immunity (Disease)</subject><subject>Immunization</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Infections</subject><subject>Lymphocytes</subject><subject>Membrane Proteins</subject><subject>Meningitis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mucosa</subject><subject>Neonates</subject><subject>Opsonization</subject><subject>Opsonophagocytosis</subject><subject>Pathogens</subject><subject>Proteins</subject><subject>Recombinant</subject><subject>Rectum</subject><subject>Sepsis</subject><subject>Serotypes</subject><subject>Strains (organisms)</subject><subject>Streptococcal Infections - prevention & control</subject><subject>Streptococcus</subject><subject>Streptococcus agalactiae</subject><subject>Streptococcus infections</subject><subject>Target recognition</subject><subject>Toxins</subject><subject>Vaccine</subject><subject>Vaccines</subject><subject>Vagina</subject><subject>Vaginal colonization</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkc9u1DAYxC0EokvLI4AscSmHBDv-k80JdStaKlXiUCpxsxzn8-JVYi-2s1V5Ch65bnfLgQsnH_yb-UYzCL2jpKaEyk-beqeNcR7qhjSkJqImrXyBFnTZsqoRdPkSLUgjecUp-XGE3qS0IYQIRrvX6Ig1oqUt7Rboz9U0zd791tkFj-9c_ok1jmDC1DuvfcYr15_hNEerDeBtDBmcxyZ4CzFh9yTO91j7Yf9pcsKTK6hea-dTxusY5i1e4ZscYZuDCcbMCZ9erm4-4p1elyNjsRvDc4YT9MrqMcHbw3uMbi--fD__Wl1_u7w6P7uuDOckV7ZrLeHAtZS6G4CDtNzYZStbZnvaGiIFtSCJNR1d9hSYZT2XTUcE6aEUwY7R6d63xP41Q8pqcsnAOGoPYU6q4VQ2kjLBC_rhH3QT5liCP1FtKZwxUSixp0wMKUWwahvdpOO9okQ9TqY26jCZepxMEaHKZEX3_uA-9xMMf1XPGxXg8x6AUsfOQVTJOPAGBleGymoI7j8nHgDdrawn</recordid><startdate>20200714</startdate><enddate>20200714</enddate><creator>dos Santos, Nayara Fernanda Barros</creator><creator>da Silva, Lukas Raposo</creator><creator>Costa, Fagner James Martins Dantas</creator><creator>de Mattos, Daniely Maranhão</creator><creator>de Carvalho, Enéas</creator><creator>Ferreira, Luís Carlos de Souza</creator><creator>Ferreira, Rita de Cássia Café</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20200714</creationdate><title>Immunization with a recombinant BibA surface protein confers immunity and protects mice against group B Streptococcus (GBS) vaginal colonization</title><author>dos Santos, Nayara Fernanda Barros ; da Silva, Lukas Raposo ; Costa, Fagner James Martins Dantas ; de Mattos, Daniely Maranhão ; de Carvalho, Enéas ; Ferreira, Luís Carlos de Souza ; Ferreira, Rita de Cássia Café</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-f97f04e4a66a9de4e6f4cf87673fb17c0651fe60fc918b1e3f3b4629050be0003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adjuvants</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Antibodies</topic><topic>Antibodies, Bacterial</topic><topic>Antigens</topic><topic>Bacteria</topic><topic>Bacterial infections</topic><topic>Cell activation</topic><topic>Chromatography</topic><topic>Colonization</topic><topic>Combined vaccines</topic><topic>Disease</topic><topic>E coli</topic><topic>Epithelial cells</topic><topic>Female</topic><topic>Immunity (Disease)</topic><topic>Immunization</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin G</topic><topic>Infections</topic><topic>Lymphocytes</topic><topic>Membrane Proteins</topic><topic>Meningitis</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mucosa</topic><topic>Neonates</topic><topic>Opsonization</topic><topic>Opsonophagocytosis</topic><topic>Pathogens</topic><topic>Proteins</topic><topic>Recombinant</topic><topic>Rectum</topic><topic>Sepsis</topic><topic>Serotypes</topic><topic>Strains (organisms)</topic><topic>Streptococcal Infections - 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Streptococcus agalactiae or group B Streptococcus (GBS) is a Gram-positive bacterium divided into ten distinct serotypes that colonizes the vaginal and rectal tracts of approximately 30% of women worldwide. GBS is the leading cause of invasive infection in newborns, causing sepsis, pneumoniae and meningitis. The main strategy to prevent GSB infection in newborns includes the use of intrapartum antibiotic therapy, which does not prevent late-onset diseases and may select resistant bacterial strains. We still do not have a vaccine formulation specific for this pathogen approved for human use. Conserved surface proteins are potential antigens that could be targets for recognition by antibodies and activation of cell opsonization. We used a serotype V GBS (GBS-V)-derived recombinant surface protein, rBibA, and evaluated the potential protective role of the induced antigen-specific antibodies after parenteral or mucosal immunizations in C57BL/6 mice. In vitro and in vivo assays demonstrated that vaccine formulations containing BibA combined with different adjuvants induced serum IgG and/or secreted IgA antibodies, leading to enhanced opsonophagocytosis of GBS-V cells and reduced invasion of epithelial cells. One BibA-based vaccine formulation adjuvanted with a nontoxic derivative of the heat-labile toxin produced by enterotoxigenic Escherichia coli (ETEC) strains was capable of inducing protection against vaginal colonization and lethal parenteral challenge with GBS-V. Serum collected from vaccinated mice conferred passive protection against vaginal colonization in naïve mice challenged with GBS-V. Taken together, the present data demonstrate that the BibA protein is a promising antigen for development of a vaccine to protect against GBS infection.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>32571719</pmid><doi>10.1016/j.vaccine.2020.05.076</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvants Animals Antibiotics Antibodies Antibodies, Bacterial Antigens Bacteria Bacterial infections Cell activation Chromatography Colonization Combined vaccines Disease E coli Epithelial cells Female Immunity (Disease) Immunization Immunoglobulin A Immunoglobulin G Infections Lymphocytes Membrane Proteins Meningitis Mice Mice, Inbred C57BL Mucosa Neonates Opsonization Opsonophagocytosis Pathogens Proteins Recombinant Rectum Sepsis Serotypes Strains (organisms) Streptococcal Infections - prevention & control Streptococcus Streptococcus agalactiae Streptococcus infections Target recognition Toxins Vaccine Vaccines Vagina Vaginal colonization |
title | Immunization with a recombinant BibA surface protein confers immunity and protects mice against group B Streptococcus (GBS) vaginal colonization |
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