Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective

Anders 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)852-863.e7
JournalImmunity
Volume53
Issue number4
DOIs
StatePublished - Oct 13 2020

Keywords

  • B cells
  • Human
  • Infection
  • Influenza B virus
  • Monoclonal antibodies
  • Neuraminidase
  • Plasmablasts

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