期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 30, 页码 17757-17763出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2004783117
关键词
influenza vaccine; chimeric hemagglutinin; monoglycosylated; broad protection; CD4 and CD8 T cell responses
资金
- Summit Program of Academia Sinica [AS-SUMMIT-108]
- Ministry of Science and Technology, Taiwan [MOST 107-0210-01-19-01, MOST 108-3114-Y-001-002]
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.
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