Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 30; pp. 17757 - 17763
• Main Authors: Liao, Hsin-Yu, Wang, Shih-Chi, Ko, Yi-An, Lin, Kuo-I, Ma, Che, Cheng, Ting-Jen Rachel, Wong, Chi-Huey
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28.07.2020
• Subjects: Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antibody-Dependent Cell Cytotoxicity; Avian flu; Biological Sciences; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Class switching; Combined vaccines; Cross Protection - immunology; Cross-protection; Cytotoxicity; Disease control; Disease Models, Animal; Glycosylation; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Humans; Immune response; Immunological memory; Influenza; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Interleukin 4; Lymphocytes; Lymphocytes T; Memory cells; Mice; Models, Molecular; Mutation; Neutralization Tests; Orthomyxoviridae - classification; Orthomyxoviridae - immunology; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - immunology; Stems; Strains (organisms); Structure-Activity Relationship; Toxicity; Vaccination; Vaccine efficacy; Vaccines; Viruses; γ-Interferon; chimeric hemagglutinin; influenza vaccine; broad protection; monoglycosylated; CD4 and CD8 T cell responses
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2004783117

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 (cHAmg) 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 cHAmg 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.