Hemagglutinin stalk-binding antibodies enhance effectiveness of neuraminidase inhibitors against influenza via Fc-dependent effector functions

Cell Rep Med. 2022 Aug 16;3(8):100718. doi: 10.1016/j.xcrm.2022.100718.

Abstract

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next-generation universal influenza vaccines. Protection provided by hemagglutinin stalk-binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

Keywords: Fc receptors; Fc-dependent effector funtions; NA inhibitors; antibodies; antibody-dependent cell cytotoxicity; antibody-dependent cellular cytotoxicity; antivirals; broadly neutralizing antibodies; influenza virus; oseltamivir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinins
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Influenza Vaccines*
  • Influenza, Human* / drug therapy
  • Neuraminidase
  • Orthomyxoviridae*

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Immunoglobulin Fc Fragments
  • Influenza Vaccines
  • Neuraminidase

Grant support