A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function.
A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function.
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DOI：
10.15252/emmm.202216208
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发表时间：
2023-02-08
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
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. Group A streptococci are experts at avoiding and disarming human antibodies with no available vaccines or antibody treatments. This study presents a novel interaction mechanism between antibodies and antigens that can induce protective immune function against group A streptococci.
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影响因子：
64.5
作者：
Freeman SA;Vega A;Riedl M;Collins RF;Ostrowski PP;Woods EC;Bertozzi CR;Tammi MI;Lidke DS;Johnson P;Mayor S;Jaqaman K;Grinstein S
通讯作者：
Grinstein S
影响因子：
4.8
作者：
Ozberk V;Pandey M;Good MF
通讯作者：
Good MF
影响因子：
3.6
作者：
Frick, IM;Mörgelin, M;Björck, L
通讯作者：
Björck, L
影响因子：
3.6
作者：
Carlsson, F;Sandin, C;Lindahl, G
通讯作者：
Lindahl, G
大小依赖性分离控制巨噬细胞对抗体调理靶标的吞噬作用。
影响因子：
64.5
作者：
Bakalar MH;Joffe AM;Schmid EM;Son S;Podolski M;Fletcher DA
通讯作者：
Fletcher DA