6V4N

Structure of human 1G05 Fab in complex with influenza virus neuraminidase from B/Phuket/3073/2013

Summary for 6V4N

• Entry DOI: 10.2210/pdb6v4n/pdb
• EMDB information: 21042
• Descriptor: Neuraminidase, Antibody Fab heavy chain, Antibody Fab light chain, ... (8 entities in total)
• Functional Keywords: viral protein, neuraminidase, structural genomics, center for structural genomics of infectious diseases, csgid
• Biological source: Influenza B virus; More
• Total number of polymer chains: 12
• Total formula weight: 405375.30

Authors

Dai, Y.N.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2019-11-28, release date: 2020-10-07, Last modification date: 2024-11-20)

Primary citation

Madsen, A.,Dai, Y.N.,McMahon, M.,Schmitz, A.J.,Turner, J.S.,Tan, J.,Lei, T.,Alsoussi, W.B.,Strohmeier, S.,Amor, M.,Mohammed, B.M.,Mudd, P.A.,Simon, V.,Cox, R.J.,Fremont, D.H.,Krammer, F.,Ellebedy, A.H.
Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective.
Immunity, 53:852-, 2020

PubMed Abstract: Influenza B virus (IBV) infections can cause severe disease in children and the elderly. Commonly used antivirals have lower clinical effectiveness against IBV compared to influenza A viruses (IAV). Neuraminidase (NA), the second major surface protein on the influenza virus, is emerging as a target of broadly protective antibodies that recognize the NA active site of IAVs. However, similarly broadly protective antibodies against IBV NA have not been identified. Here, we isolated and characterized human monoclonal antibodies (mAbs) that target IBV NA from an IBV-infected patient. Two mAbs displayed broad and potent capacity to inhibit IBV NA enzymatic activity, neutralize the virus in vitro, and protect against lethal IBV infection in mice in prophylactic and therapeutic settings. These mAbs inserted long CDR-H3 loops into the NA active site, engaging residues highly conserved among IBV NAs. These mAbs provide a blueprint for the development of improved vaccines and therapeutics against IBVs.

PubMed: 32976769
DOI: 10.1016/j.immuni.2020.08.015

Experimental method

ELECTRON MICROSCOPY (2.5 Å)