A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function

Autor: Wael Bahnan, Lotta Happonen, Hamed Khakzad, Vibha Kumra Ahnlide, Therese deNeergaard, Sebastian Wrighton, Oscar André, Eleni Bratanis, Di Tang, Thomas Hellmark, Lars Björck, Oonagh Shannon, Lars Malmström, Johan Malmström, Pontus Nordenfelt
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 15, Iss 2, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 1757-4684
1757-4676
DOI: 10.15252/emmm.202216208
Popis: 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.
Databáze: Directory of Open Access Journals
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