Han Lifen, Chen Cong, Han Xianlin, Lin Shujin, Ao Xiulan, Han Xiao, Wang Jianmin, Ye Hanhui
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China.
College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China.
Comput Struct Biotechnol J. 2019 Mar 23;17:475-483. doi: 10.1016/j.csbj.2019.03.009. eCollection 2019.
Influenza A virus are a persistent and significant threat to human health, and current vaccines do not provide sufficient protection due to antigenic drift, which allows influenza viruses to easily escape immune surveillance and antiviral drug activity. Influenza hemagglutinin (HA) is a glycoprotein needed for the entry of enveloped influenza viruses into host cells and is a potential target for anti-influenza humoral immune responses. In recent years, a number of broadly neutralizing antibodies (bnAbs) have been isolated, and their relative structural information obtained from the crystallization of influenza antigens in complex with bnAbs has provided some new insights into future influenza vaccine research. Here, we review the current knowledge of the HA-targeted bnAbs and the structure-based mechanisms contributing to neutralization. We also discuss the potential for this structure-based approach to overcome the challenge of obtaining a highly desired "universal" influenza vaccine, especially on small proteins and peptides.
甲型流感病毒对人类健康构成持续且重大的威胁,由于抗原漂移,目前的疫苗无法提供足够的保护,抗原漂移使得流感病毒能够轻易逃避免疫监视和抗病毒药物活性。流感血凝素(HA)是包膜流感病毒进入宿主细胞所需的糖蛋白,是抗流感体液免疫反应的潜在靶点。近年来,已分离出多种广泛中和抗体(bnAbs),并且通过流感抗原与bnAbs复合物的结晶获得的它们的相关结构信息为未来的流感疫苗研究提供了一些新见解。在这里,我们综述了目前针对HA的bnAbs的知识以及促成中和作用的基于结构的机制。我们还讨论了这种基于结构的方法克服获得高度理想的“通用”流感疫苗挑战的潜力,特别是在小蛋白质和肽方面。