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TitleHuman anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo.
Journal, issue, pagesImmunity, Vol. 56, Issue 8, Page 1927-11938.e8, Year 2023
Publish dateAug 8, 2023
AuthorsLena Hansen / Meagan McMahon / Hannah L Turner / Xueyong Zhu / Jackson S Turner / Gabriel Ozorowski / Daniel Stadlbauer / Juha Vahokoski / Aaron J Schmitz / Amena A Rizk / Wafaa B Alsoussi / Shirin Strohmeier / Wenli Yu / José Alberto Choreño-Parra / Luis Jiménez-Alvarez / Alfredo Cruz-Lagunas / Joaquín Zúñiga / Philip A Mudd / Rebecca J Cox / Ian A Wilson / Andrew B Ward / Ali H Ellebedy / Florian Krammer /
PubMed AbstractNeuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA ...Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.
External linksImmunity / PubMed:37506693 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.2 - 3.1 Å
Structure data

EMDB-27920, PDB-8e6j:
3H03 Fab in complex with influenza virus neuraminidase from A/Brevig Mission/1/1918 (H1N1)
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-27921, PDB-8e6k:
2H08 Fab in complex with influenza virus neuraminidase from A/Brevig Mission/1/1918 (H1N1)
Method: EM (single particle) / Resolution: 3.1 Å

PDB-8eqa:
Crystal structure of human anti-N1 neuraminidase 2H08 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.55 Å

PDB-8eqc:
Crystal structure of human anti-N1 neuraminidase 3H03 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-PO4:
PHOSPHATE ION / Phosphate

Source
  • influenza a virus (a/brevig mission/1/1918(h1n1))
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / influenza / monoclonal antibody / H1N1 / cross-reactive antibody / IMMUNE SYSTEM / antibody / neuraminidase / broad protection / pandemic

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