A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function
Abstract Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococca...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-12-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202216208 |
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| author | Wael Bahnan Lotta Happonen Hamed Khakzad Vibha Kumra Ahnlide Therese de Neergaard Sebastian Wrighton Oscar André Eleni Bratanis Di Tang Thomas Hellmark Lars Björck Oonagh Shannon Lars Malmström Johan Malmström Pontus Nordenfelt |
| author_facet | Wael Bahnan Lotta Happonen Hamed Khakzad Vibha Kumra Ahnlide Therese de Neergaard Sebastian Wrighton Oscar André Eleni Bratanis Di Tang Thomas Hellmark Lars Björck Oonagh Shannon Lars Malmström Johan Malmström Pontus Nordenfelt |
| author_sort | Wael Bahnan |
| collection | DOAJ |
| description | Abstract Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity in the central region of the surface‐bound M protein. Such antibodies are typically non‐opsonic. However, one antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody primarily interacts through a bivalent dual‐Fab cis mode, where the Fabs bind to two distinct epitopes in the M protein. The dual‐Fab cis‐binding phenomenon is conserved across different groups of M types. In contrast, other antibodies binding with normal single‐Fab mode to the same region cannot bypass the M protein's virulent effects. A broadly binding, protective monoclonal antibody could be a candidate for anti‐streptococcal therapy. Our findings highlight the concept of dual‐Fab cis binding as a means to access conserved, and normally non‐opsonic regions, regions for protective antibody targeting. |
| format | Article |
| id | doaj-art-2bcb7da2abe14c5fb5c5a0341f1349d2 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-2bcb7da2abe14c5fb5c5a0341f1349d22025-08-24T11:43:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-12-0115212110.15252/emmm.202216208A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune functionWael Bahnan0Lotta Happonen1Hamed Khakzad2Vibha Kumra Ahnlide3Therese de Neergaard4Sebastian Wrighton5Oscar André6Eleni Bratanis7Di Tang8Thomas Hellmark9Lars Björck10Oonagh Shannon11Lars Malmström12Johan Malmström13Pontus Nordenfelt14Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityEquipe Signalisation Calcique et Infections Microbiennes, École Normale Supérieure Paris‐SaclayDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDepartment of Clinical Sciences Lund, Division of Nephrology, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityAbstract Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity in the central region of the surface‐bound M protein. Such antibodies are typically non‐opsonic. However, one antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody primarily interacts through a bivalent dual‐Fab cis mode, where the Fabs bind to two distinct epitopes in the M protein. The dual‐Fab cis‐binding phenomenon is conserved across different groups of M types. In contrast, other antibodies binding with normal single‐Fab mode to the same region cannot bypass the M protein's virulent effects. A broadly binding, protective monoclonal antibody could be a candidate for anti‐streptococcal therapy. Our findings highlight the concept of dual‐Fab cis binding as a means to access conserved, and normally non‐opsonic regions, regions for protective antibody targeting.https://doi.org/10.15252/emmm.202216208dual‐Fabimmune functionmonoclonalsStreptococcustherapeutics |
| spellingShingle | Wael Bahnan Lotta Happonen Hamed Khakzad Vibha Kumra Ahnlide Therese de Neergaard Sebastian Wrighton Oscar André Eleni Bratanis Di Tang Thomas Hellmark Lars Björck Oonagh Shannon Lars Malmström Johan Malmström Pontus Nordenfelt A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function EMBO Molecular Medicine dual‐Fab immune function monoclonals Streptococcus therapeutics |
| title | A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function |
| title_full | A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function |
| title_fullStr | A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function |
| title_full_unstemmed | A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function |
| title_short | A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function |
| title_sort | human monoclonal antibody bivalently binding two different epitopes in streptococcal m protein mediates immune function |
| topic | dual‐Fab immune function monoclonals Streptococcus therapeutics |
| url | https://doi.org/10.15252/emmm.202216208 |
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