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

Immunity. 2020 Oct 13;53(4):852-863.e7. doi: 10.1016/j.immuni.2020.08.015. Epub 2020 Sep 24.


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.

Keywords: B cells; Human; Infection; Influenza B virus; Monoclonal antibodies; Neuraminidase; Plasmablasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / immunology*
  • Catalytic Domain / immunology*
  • Cell Line
  • Dogs
  • Female
  • HEK293 Cells
  • Humans
  • Influenza A virus / immunology
  • Influenza B virus / immunology*
  • Influenza, Human / immunology
  • Leukocytes, Mononuclear / immunology
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neuraminidase / immunology*
  • Orthomyxoviridae Infections / immunology
  • Viral Proteins / immunology*


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Viral Proteins
  • Neuraminidase