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Nat Microbiol. 2017 Oct;2(10):1415-1424. doi: 10.1038/s41564-017-0011-8. Epub 2017 Aug 21.

Broadly protective murine monoclonal antibodies against influenza B virus target highly conserved neuraminidase epitopes.

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
2
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
3
Center for Cancer Research, National Cancer Institute Building 50, Room 4306, National Institutes of Health, Bethesda, MD 20892-8008, USA.
4
Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
5
Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA. florian.krammer@mssm.edu.

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.

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PMID:
28827718
PMCID:
PMC5819343
DOI:
10.1038/s41564-017-0011-8
[Indexed for MEDLINE]
Free PMC Article

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