Universal antibodies and their applications to the quantitative determination of virtually all subtypes of the influenza A viral hemagglutinins

被引:66
作者
Chun, Stella [1 ,5 ]
Li, Changgui [2 ]
Van Domselaar, Gary [4 ]
Wang, Junzhi [2 ]
Farnsworth, Aaron [1 ]
Cui, Xiaoyu [2 ]
Rode, Harold [3 ]
Cyr, Terry D. [1 ]
He, Runtao [4 ]
Li, Xuguang [1 ,5 ]
机构
[1] Hlth Canada, Biol & Genet Therapies Directorate, Biol Res Ctr, HPFB, Ottawa, ON K1A 0L2, Canada
[2] State Food & Drug Adm, Natl Inst Control Pharmaceut & Biol Prod, Beijing, Peoples R China
[3] Hlth Canada, Biol & Genet Therapies Directorate, Ctr Biol Evaluat, HPFB, Ottawa, ON K1A 0L2, Canada
[4] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
[5] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada
关键词
Influenza vaccine; Fusion peptide; Protein unfolding; Potency testing; Universal antibodies;
D O I
10.1016/j.vaccine.2008.09.015
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The fusion peptide is the only universally conserved sequence in the hamagglutinins of all 16 subtypes of influenza A and two genetic lineages Of influenza B viruses. Here, peptides selected by bioinformatics approach were modified and conjugated to overcome serious technical hurdles such as the high hydrophobicity and weak immunogenicity of the viral fusion peptides. Antibodies generated against fusion peptides demonstrated remarkable specificity against the viral sequences and robustness of quantitatively analyzing the viral hemagglutinins even under stringent conditions. As quantitatively revealed by anti body-binding experiments, the fusion peptides of diverse hemagglutinins are exposed to the same degree upon unfolding at neutral pH to the physiologically fusogenic state. To our knowledge, this is the first report on the quantitative determination of virtually all influenza vaccines using a single universal antibody. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:6068 / 6076
页数:9
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