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

被引:46
作者
Doyle, Tracey M. [1 ,6 ]
Li, Changgui [2 ]
Bucher, Doris J. [5 ]
Hashem, Anwar M. [1 ,3 ,4 ,6 ]
Van Domselaar, Gary [7 ]
Wang, Junzhi [2 ]
Farnsworth, Aaron [1 ]
She, Yi-Min [1 ]
Cyr, Terry [1 ]
He, Runtao [7 ]
Brown, Earl G. [6 ]
Hurt, Aeron C. [8 ]
Li, Xuguang [1 ,6 ]
机构
[1] Hlth Canada, Ctr Vaccine Evaluat, Biol & Genet Therapies Directorate, HPFB, Ottawa, ON K1A 0L2, Canada
[2] Natl Inst Food & Drug Control, Beijing, Peoples R China
[3] King Abdulaziz Univ, Dept Med Microbiol & Parasitol, Fac Med, Jeddah 13, Saudi Arabia
[4] King Abdulaziz Univ, King Fand Ctr Med Res, Special Infect Agents Unit, Jeddah 13, Saudi Arabia
[5] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA
[6] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada
[7] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
[8] WHO Collaborating Ctr Reference & Res Influenza, North Melbourne, Vic 3051, Australia
关键词
Neuraminidase; Universal antibody; Vaccination; Cross-protection; Influenza B; UNIVERSAL ANTIBODIES; REDUCED SENSITIVITY; VIRAL NEURAMINIDASE; A VIRUS; INHIBITOR; SUBTYPES;
D O I
10.1016/j.bbrc.2013.10.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:226 / 229
页数:4
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