A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains |
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Authors: | Tracey M Doyle Changgui Li Doris J Bucher Anwar M Hashem Gary Van Domselaar Junzhi Wang Aaron Farnsworth Yi-Min She Terry Cyr Runtao He Earl G Brown Aeron C Hurt Xuguang Li |
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Institution: | 1. Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada;2. National Institutes for Food and Drug Control, Beijing, China;3. Department of Medical Microbiology and Parasitology, Faculty of Medicine and Special Infectious Agents Unit, King Fahd Center for Medical Research, King Abdulaziz University, 13 Jeddah, Saudi Arabia;4. Department of Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, United States;5. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada;6. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada;g WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St., North Melbourne, Victoria 3051, Australia |
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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. |
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Keywords: | Neuraminidase Universal antibody Vaccination Cross-protection Influenza B |
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