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Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 106, 2009, 41, S. 17481-17486 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Gallorini, Simona Berti, Francesco Mancuso, Giuseppe Cozzi, Roberta Tortoli, Marco Volpini, Gianfranco Telford, John L. Beninati, Concetta Maione, Domenico Wack, Andreas Gallorini, Simona Berti, Francesco Mancuso, Giuseppe Cozzi, Roberta Tortoli, Marco Volpini, Gianfranco Telford, John L. Beninati, Concetta Maione, Domenico Wack, Andreas |
|---|---|
| author |
Gallorini, Simona Berti, Francesco Mancuso, Giuseppe Cozzi, Roberta Tortoli, Marco Volpini, Gianfranco Telford, John L. Beninati, Concetta Maione, Domenico Wack, Andreas |
| spellingShingle |
Gallorini, Simona Berti, Francesco Mancuso, Giuseppe Cozzi, Roberta Tortoli, Marco Volpini, Gianfranco Telford, John L. Beninati, Concetta Maione, Domenico Wack, Andreas Proceedings of the National Academy of Sciences Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides Multidisciplinary |
| author_sort |
gallorini, simona |
| spelling |
Gallorini, Simona Berti, Francesco Mancuso, Giuseppe Cozzi, Roberta Tortoli, Marco Volpini, Gianfranco Telford, John L. Beninati, Concetta Maione, Domenico Wack, Andreas 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0903313106 <jats:p>Group B<jats:italic>Streptococcus</jats:italic>(GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2). To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.</jats:p> Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides Proceedings of the National Academy of Sciences |
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| title |
Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_unstemmed |
Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_full |
Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_fullStr |
Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_full_unstemmed |
Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_short |
Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_sort |
toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.0903313106 |
| publishDate |
2009 |
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17481-17486 |
| description |
<jats:p>Group B<jats:italic>Streptococcus</jats:italic>(GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2). To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.</jats:p> |
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| author | Gallorini, Simona, Berti, Francesco, Mancuso, Giuseppe, Cozzi, Roberta, Tortoli, Marco, Volpini, Gianfranco, Telford, John L., Beninati, Concetta, Maione, Domenico, Wack, Andreas |
| author_facet | Gallorini, Simona, Berti, Francesco, Mancuso, Giuseppe, Cozzi, Roberta, Tortoli, Marco, Volpini, Gianfranco, Telford, John L., Beninati, Concetta, Maione, Domenico, Wack, Andreas, Gallorini, Simona, Berti, Francesco, Mancuso, Giuseppe, Cozzi, Roberta, Tortoli, Marco, Volpini, Gianfranco, Telford, John L., Beninati, Concetta, Maione, Domenico, Wack, Andreas |
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| description | <jats:p>Group B<jats:italic>Streptococcus</jats:italic>(GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2). To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.</jats:p> |
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| imprint_str_mv | Proceedings of the National Academy of Sciences, 2009 |
| institution | DE-14, DE-105, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1 |
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| spelling | Gallorini, Simona Berti, Francesco Mancuso, Giuseppe Cozzi, Roberta Tortoli, Marco Volpini, Gianfranco Telford, John L. Beninati, Concetta Maione, Domenico Wack, Andreas 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0903313106 <jats:p>Group B<jats:italic>Streptococcus</jats:italic>(GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2). To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.</jats:p> Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides Proceedings of the National Academy of Sciences |
| spellingShingle | Gallorini, Simona, Berti, Francesco, Mancuso, Giuseppe, Cozzi, Roberta, Tortoli, Marco, Volpini, Gianfranco, Telford, John L., Beninati, Concetta, Maione, Domenico, Wack, Andreas, Proceedings of the National Academy of Sciences, Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides, Multidisciplinary |
| title | Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_full | Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_fullStr | Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_full_unstemmed | Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_short | Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_sort | toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| title_unstemmed | Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.0903313106 |