Chun Stella, Li Changgui, Van Domselaar Gary, Wang Junzhi, Farnsworth Aaron, Cui Xiaoyu, Rode Harold, Cyr Terry D, He Runtao, Li Xuguang
Centre for Biologics Research, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada.
Vaccine. 2008 Nov 11;26(48):6068-76. doi: 10.1016/j.vaccine.2008.09.015.
The fusion peptide is the only universally conserved sequence in the hemagglutinins 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 antibody-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.
融合肽是甲型流感病毒所有16个亚型以及乙型流感病毒两个遗传谱系的血凝素中唯一普遍保守的序列。在此,通过生物信息学方法筛选出的肽段经过修饰和偶联,以克服诸如病毒融合肽疏水性高和免疫原性弱等严重技术障碍。针对融合肽产生的抗体对病毒序列具有显著的特异性,并且即使在严格条件下也能对病毒血凝素进行稳健的定量分析。抗体结合实验定量显示,在中性pH下展开至生理融合状态时,不同血凝素的融合肽暴露程度相同。据我们所知,这是第一份关于使用单一通用抗体对几乎所有流感疫苗进行定量测定的报告。