Zhang Limin, Chen Junyu, Shen Chenguang, Wang Guosong, Lu Zhen, Zeng Dian, Gao Ying, Chen Huiqing, Xia Ningshao, Chen Yixin
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, China.
Vaccines (Basel). 2022 Aug 11;10(8):1304. doi: 10.3390/vaccines10081304.
Recent efforts have been directed toward the development of universal influenza vaccines inducing broadly neutralizing antibodies to conserved antigenic supersites of Hemagglutinin (HA). Although several studies raise the importance of glycosylation in HA antigen design, whether this theory can be widely confirmed remains unclear; which influenza HA with an altered glycosylation profile could impact the amplitude and focus of the host immune response. Here, we evaluated the characteristics and efficacy of deglycosylated modified HA proteins, including monoglycosylated HA (HA), unglycosylated HA (HA), and fully glycosylated HA (HA), without treatment with H3N2 Wisconsin/67/2005. Our results showed that HA could induce a cross-strain protective immune response in mice against both H3N2 and H7N9 subtypes with better antibody-dependent cellular cytotoxicity (ADCC) than the HA- and HA-immunized groups, which suggested that highly conserved epitopes that were masked by surface glycosylation may be exposed and thus promote the induction of broad antibodies that recognize the hidden epitopes. This strategy may also supplement the direction of deglycosylated modified HA for universal influenza vaccines.
近期的研究致力于开发通用流感疫苗，该疫苗可诱导产生针对血凝素（HA）保守抗原超位点的广泛中和抗体。尽管多项研究凸显了糖基化在HA抗原设计中的重要性，但这一理论能否得到广泛证实仍不明确；改变糖基化谱的哪种流感HA会影响宿主免疫反应的强度和靶向性。在此，我们评估了去糖基化修饰的HA蛋白的特性和功效，包括单糖基化HA（HA）、无糖基化HA（HA）和完全糖基化HA（HA），未用H3N2威斯康星/67/2005进行处理。我们的结果表明，HA能在小鼠体内诱导针对H3N2和H7N9亚型的跨毒株保护性免疫反应，其抗体依赖性细胞毒性（ADCC）比HA免疫组和HA免疫组更好，这表明被表面糖基化掩盖的高度保守表位可能会暴露出来，从而促进诱导识别隐藏表位的广谱抗体。该策略也可为通用流感疫苗的去糖基化修饰HA方向提供补充。
