title: A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains.
abstract: All influenza viral neuraminidases (NA) of both type A and B viruses have only one universally conserved sequence located between amino acids 222-230. A monoclonal antibody against this region has been previously reported to provide broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory effect against influenza B viral NA remained unknown. Here, we report that the monoclonal antibody provides a broad inhibition against various strains of influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the growth and NA enzymatic activity of two drug resistant influenza B strains (E117D and D197E) are also inhibited by the antibody even though these two mutations are conformationally proximal to the universal epitope. Collectively, these data suggest that this unique, highly-conserved linear sequence in viral NA is exposed sufficiently to allow access by inhibitory antibody during the course of infection; it could represent a potential target for antiviral agents and vaccine-induced immune responses against diverse strains of type B influenza virus.
authors.affiliation: Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Doyle
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Bucher
authors.forename: Anwar M
authors.initials: AM
authors.lastname: Hashem
authors.forename: Gary
authors.initials: G
authors.lastname: Van Domselaar
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Aaron
authors.initials: A
authors.lastname: Farnsworth
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: She
authors.forename: Terry
authors.initials: T
authors.lastname: Cyr
authors.forename: Runtao
authors.initials: R
authors.lastname: He
authors.forename: Earl G
authors.initials: EG
authors.lastname: Brown
authors.forename: Aeron C
authors.initials: AC
authors.lastname: Hurt
authors.forename: Xuguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology; D017124:Conserved Sequence; D004285:Dogs; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D009981:Influenza B virus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D009439:Neuraminidase
keywords: Cross-protection; Influenza B; Neuraminidase; Universal antibody; Vaccination