文章基本信息

标题：Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes
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作者：Hsin-Yu Liao ; Shih-Chi Wang ; Yi-An Ko 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：30
页码：17757-17763
DOI：10.1073/pnas.2004783117
出版社：The National Academy of Sciences of the United States of America
摘要：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 better 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-γ, IL-4, and CD8⁺ memory T cells produced.
关键词：influenza vaccine ; chimeric hemagglutinin ; monoglycosylated ; broad protection ; CD4 and CD8 T cell responses