A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains

• Published in: Biochemical and biophysical research communications 2013-11, Vol.441 (1), p.226-229
• Main Authors: Doyle, Tracey M., Li, Changgui, Bucher, Doris J., Hashem, Anwar M., Van Domselaar, Gary, Wang, Junzhi, Farnsworth, Aaron, She, Yi-Min, Cyr, Terry, He, Runtao, Brown, Earl G., Hurt, Aeron C., Li, Xuguang
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Viral - immunology; Conserved Sequence; Cross-protection; Dogs; Drug Resistance, Viral - drug effects; Drug Resistance, Viral - genetics; Drug Resistance, Viral - immunology; Epitopes - chemistry; Epitopes - immunology; Humans; Influenza B; Influenza B virus - drug effects; Influenza B virus - enzymology; Influenza B virus - growth & development; Influenza B virus - immunology; Influenza virus; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Madin Darby Canine Kidney Cells; Models, Molecular; Molecular Sequence Data; Mutation - genetics; Neuraminidase; Neuraminidase - antagonists & inhibitors; Neuraminidase - chemistry; Neuraminidase - immunology; Universal antibody; Vaccination
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.10.041

•The antigenic epitopes of influenza B viral neuraminidase evolve unpredictably.•A monoclonal targeting the only universally conserved epitope is evaluated.•The antibody inhibits both wild-type and drug resistant strains.•First report suggesting the universal epitope is an attractive target for antiviral and vaccination. 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.