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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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2022-12-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216208 |
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| Summary: | 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. |
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| ISSN: | 1757-4676 1757-4684 |