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Proc Natl Acad Sci U S A . Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strain

tetano

Editor, Senior Moderator
Proc Natl Acad Sci U S A


. 2020 Jul 15;202004783.
doi: 10.1073/pnas.2004783117. Online ahead of print.
Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes


Hsin-Yu Liao[SUP] 1 [/SUP], Shih-Chi Wang[SUP] 1 [/SUP], Yi-An Ko[SUP] 1 [/SUP], Kuo-I Lin[SUP] 1 [/SUP], Che Ma[SUP] 1 [/SUP], Ting-Jen Rachel Cheng[SUP] 1 [/SUP], Chi-Huey Wong[SUP] 2 3 [/SUP]



Affiliations

Abstract

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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses. Interestingly, the monoglycosylated cHA (cHA[SUB]mg[/SUB]) 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[SUB]mg[/SUB] vaccine combined with a glycolipid adjuvant designed for class switch further enhanced the vaccine efficacy with more IFN-γ, IL-4, and CD8[SUP]+[/SUP] memory T cells produced.

Keywords: CD4 and CD8 T cell responses; broad protection; chimeric hemagglutinin; influenza vaccine; monoglycosylated.
 
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