Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus
Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus
复制标题
DOI：
10.1016/j.bbrc.2010.11.030
复制
发表时间：
2010-12-10
影响因子：
3.1
通讯作者：
Li, Xuguang
中科院分区：
文献类型：
--
作者：
Hashem, Anwar M.;Van Domselaar, Gary;Li, Xuguang
流感病毒血凝素融合肽通过促进病毒与靶细胞之间的膜融合，在病毒进入过程中起关键作用。由于融合肽是所有甲型和乙型流感病毒中唯一普遍保守的表位，它可能是疫苗诱导免疫反应的一个有吸引力的靶点。我们之前报道过，针对融合肽n端前14个氨基酸的抗体可以与几乎所有流感病毒株结合，并在胚胎蛋中生产的疫苗中量化血凝素。在这里，我们证明了这些通用抗体结合病毒血凝素的天然构象呈现在受感染的哺乳动物细胞培养和中和多种亚型的病毒通过抑制ph依赖的融合病毒和细胞膜。这些结果表明，病毒血凝素中这一独特的、高度保守的线性序列在感染过程中被暴露到足以受到抗体的攻击，值得进一步研究，因为它在预防不同流感病毒株方面具有潜在的重要性。英国皇家版权所有(C) 2010出版的爱思唯尔公司。版权所有。
The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.