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TitleHuman Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective.
Journal, issue, pagesImmunity, Vol. 53, Issue 4, Page 852-863.e7, Year 2020
Publish dateOct 13, 2020
AuthorsAnders Madsen / Ya-Nan Dai / Meagan McMahon / Aaron J Schmitz / Jackson S Turner / Jessica Tan / Tingting Lei / Wafaa B Alsoussi / Shirin Strohmeier / Mostafa Amor / Bassem M Mohammed / Philip A Mudd / Viviana Simon / Rebecca J Cox / Daved H Fremont / Florian Krammer / Ali H Ellebedy /
PubMed AbstractInfluenza 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). ...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.
External linksImmunity / PubMed:32976769 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 2.8 Å
Structure data

21042

6v4n

EMDB-21042, PDB-6v4n:
Structure of human 1G05 Fab in complex with influenza virus neuraminidase from B/Phuket/3073/2013
Method: EM (single particle) / Resolution: 2.5 Å

21043

6v4o

EMDB-21043, PDB-6v4o:
Structure of human 2E01 Fab in complex with influenza virus neuraminidase from B/Phuket/3073/2013
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-BMA:
beta-D-mannopyranose

ChemComp-HOH:
WATER

Source
  • influenza b virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / neuraminidase / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID

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