Universal anti-neuraminidase antibody inhibiting all influenza A subtypes

被引:98
作者
Doyle, Tracey M. [1 ,6 ,7 ]
Hashem, Anwar M. [1 ,3 ,4 ]
Li, Changgui [5 ]
Van Domselaar, Gary [2 ]
Larocque, Louise [1 ]
Wang, Junzhi [5 ]
Smith, Daryl [1 ]
Cyr, Terry [1 ]
Farnsworth, Aaron [1 ]
He, Runtao [2 ]
Hurt, Aeron C. [8 ]
Brown, Earl G. [6 ,7 ]
Li, Xuguang [1 ,6 ,7 ]
机构
[1] Hlth Canada, HPFB, Biol & Genet Therapies Directorate, Ctr Vaccine Evaluat, Ottawa, ON K1A 0K9, Canada
[2] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
[3] King Abdulaziz Univ, Fac Med, Dept Med Microbiol & Parasitol, Jeddah, Saudi Arabia
[4] King Abdulaziz Univ, King Fahd Ctr Med Res, Special Infect Agents Unit, Jeddah, Saudi Arabia
[5] Natl Inst Food & Drug Control, Beijing, Peoples R China
[6] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada
[7] Univ Ottawa, Emerging Pathogens Res Ctr, Ottawa, ON K1H 8M5, Canada
[8] WHO Collaborating Ctr Reference & Res Influenza, North Melbourne, Vic 3051, Australia
关键词
Neuraminidase; Universal antibody; Cross-protection; VIRUS-INFECTION; VIRAL NEURAMINIDASE; BROAD-SPECTRUM; PANDEMIC H1N1; HEMAGGLUTININ; PROTECTION; IMMUNIZATION; IMMUNITY; VACCINE; ENTRY;
D O I
10.1016/j.antiviral.2013.09.018
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb. Moreover, the antibody also provided heterosubtypic protection in mice challenged with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II viruses, respectively. Furthermore, we report amino acid residues 1222 and E227, located in close proximity to the active site, are indispensable for inhibition by this antibody. This unique, highly-conserved linear sequence in viral NA could be an attractive immunological target for protection against diverse strains of influenza viruses. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:567 / 574
页数:8
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