Broadly protective murine monoclonal antibodies against influenza B virus target highly conserved neuraminidase epitopes
Open Access
- 21 August 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Microbiology
- Vol. 2 (10), 1415-1424
- https://doi.org/10.1038/s41564-017-0011-8
Abstract
A substantial proportion of influenza-related childhood deaths are due to infection with influenza B viruses, which co-circulate in the human population as two antigenically distinct lineages defined by the immunodominant receptor binding protein, haemagglutinin. While broadly cross-reactive, protective monoclonal antibodies against the haemagglutinin of influenza B viruses have been described, none targeting the neuraminidase, the second most abundant viral glycoprotein, have been reported. Here, we analyse a panel of five murine anti-neuraminidase monoclonal antibodies that demonstrate broad binding, neuraminidase inhibition, in vitro antibody-dependent cell-mediated cytotoxicity and in vivo protection against influenza B viruses belonging to both haemagglutinin lineages and spanning over 70 years of antigenic drift. Electron microscopic analysis of two neuraminidase–antibody complexes shows that the conserved neuraminidase epitopes are located on the head of the molecule and that they are distinct from the enzymatic active site. In the mouse model, one therapeutic dose of antibody 1F2 was more protective than the current standard of treatment, oseltamivir, given twice daily for six days.Keywords
This publication has 57 references indexed in Scilit:
- Influenza A penetrates host mucus by cleaving sialic acids with neuraminidaseVirology Journal, 2013
- Human Monoclonal Antibodies Broadly Neutralizing against Influenza B VirusPLoS Pathogens, 2013
- RELION: Implementation of a Bayesian approach to cryo-EM structure determinationJournal of Structural Biology, 2012
- A Carboxy-Terminal Trimerization Domain Stabilizes Conformational Epitopes on the Stalk Domain of Soluble Recombinant Hemagglutinin SubstratesPLOS ONE, 2012
- A Pan-H1 Anti-Hemagglutinin Monoclonal Antibody with Potent Broad-Spectrum EfficacyIn VivoJournal of Virology, 2012
- Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different HemagglutininsPLoS Pathogens, 2010
- Long time trends in influenza-like illness and associated determinants in The NetherlandsEpidemiology and Infection, 2008
- Crystal Structure of Unliganded Influenza B Virus HemagglutininJournal of Virology, 2008
- Exploration of the emergence of the Victoria lineage of influenza B virusArchiv für die gesamte Virusforschung, 2006
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004