||79 (Research article)
||Wael Bahnan, Lotta Happonen, Hamed Khakzad, Vibha Kumra Ahnlide, Therese de Neergaard, Sebastian Wrighton, Oscar Andre, 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 Mol Med (2022) e16208
||5 citations (journal impact: 12.137)
||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.