6S0Y

Nanobody targeting influenza A matrix protein 2 ectodomain (M2e)

Summary for 6S0Y

• Entry DOI: 10.2210/pdb6s0y/pdb
• Descriptor: M2e-VHH-23m, Matrix protein 2 (3 entities in total)
• Functional Keywords: influenza a, fc gamma receptor iv, m2 matrix protein, nanobody, antiviral protein
• Biological source: Lama glama; More
• Total number of polymer chains: 4
• Total formula weight: 31629.21

Authors

Van Molle, I.,De Vlieger, D.,Schepens, B.,Remaut, H.,Saelens, X. (deposition date: 2019-06-18, release date: 2020-01-22, Last modification date: 2024-10-09)

Primary citation

De Vlieger, D.,Hoffmann, K.,Van Molle, I.,Nerinckx, W.,Van Hoecke, L.,Ballegeer, M.,Creytens, S.,Remaut, H.,Hengel, H.,Schepens, B.,Saelens, X.
Selective Engagement of Fc gamma RIV by a M2e-Specific Single Domain Antibody Construct Protects Against Influenza A Virus Infection.
Front Immunol, 10:2920-2920, 2019

PubMed Abstract: Lower respiratory tract infections, such as infections caused by influenza A viruses, are a constant threat for public health. Antivirals are indispensable to control disease caused by epidemic as well as pandemic influenza A. We developed a novel anti-influenza A virus approach based on an engineered single-domain antibody (VHH) construct that can selectively recruit innate immune cells to the sites of virus replication. This protective construct comprises two VHHs. One VHH binds with nanomolar affinity to the conserved influenza A matrix protein 2 (M2) ectodomain (M2e). Co-crystal structure analysis revealed that the complementarity determining regions 2 and 3 of this VHH embrace M2e. The second selected VHH specifically binds to the mouse Fcγ Receptor IV (FcγRIV) and was genetically fused to the M2e-specific VHH, which resulted in a bi-specific VHH-based construct that could be efficiently expressed in . In the presence of M2 expressing or influenza A virus-infected target cells, this single domain antibody construct selectively activated the mouse FcγRIV. Moreover, intranasal delivery of this bispecific FcγRIV-engaging VHH construct protected wild type but not γ mice against challenge with an H3N2 influenza virus. These results provide proof of concept that VHHs directed against a surface exposed viral antigen can be readily armed with effector functions that trigger protective antiviral activity beyond direct virus neutralization.

PubMed: 31921179
DOI: 10.3389/fimmu.2019.02920

Experimental method

X-RAY DIFFRACTION (1.81 Å)