Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes
Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes
复制标题
DOI：
10.1073/pnas.2004783117
复制
发表时间：
2020-07-28
影响因子：
11.1
通讯作者：
Wong, Chi-Huey
中科院分区：
文献类型：
--
作者：
Liao, Hsin-Yu;Wang, Shih-Chi;Wong, Chi-Huey
疫苗接种已被用来控制季节性流感的传播;然而，病毒继续进化并通过突变和增加糖基化来逃避宿主免疫反应。已经致力于开发对多种流感毒株和亚型具有广泛保护活性的通用疫苗。在这里，我们报告了各种嵌合疫苗的设计和评价的基础上最常见的禽流感H5和人流感H1序列。在这些构建体中，以共有H5作为球状头部和共有H1作为茎的嵌合HA（cHA）疫苗显示出广泛的保护性CD 4（+）和CD 8（+）T细胞应答。有趣的是，在每个糖基上具有GlcNAc的单糖基化cHA（cHA（mg））疫苗诱导更多的干细胞特异性抗体，具有更高的抗体依赖性细胞毒性（ADCC），以及针对H1、H3、H5和H7毒株和亚型的更好的中和和更强的交叉保护活性。此外，cHA（mg）疫苗与设计用于类别转换的糖脂佐剂组合进一步增强了疫苗效力，产生了更多的IFN-γ、IL-4和CD 8（+）记忆T细胞。
Vaccination has been used to control the spread of seasonal flu; however, the virus continues to evolve and escape from host immune response through mutation and increasing glycosylation. Efforts have been directed toward development of a universal vaccine with broadly protective activity against multiple influenza strains and subtypes. Here we report the design and evaluation of various chimeric vaccines based on the most common avian influenza H5 and human influenza H1 sequences. Of these constructs, the chimeric HA (cHA) vaccine with consensus H5 as globular head and consensus H1 as stem was shown to elicit broadly protective CD4(+) and CD8(+) T cell responses. Interestingly, the monoglycosylated cHA (cHA(mg)) vaccine with GlcNAc on each glycosite induced more stem-specific antibodies, with higher antibody-dependent cellular cytotoxicity (ADCC), and bet-ter neutralizing and stronger cross-protection activities against H1, H3, H5, and H7 strains and subtypes. Moreover, the cHA(mg) vaccine combined with a glycolipid adjuvant designed for class switch further enhanced the vaccine efficacy with more IFN-gamma, IL-4, and CD8(+) memory T cells produced.