iScience . Synergistic effect of non-neutralizing antibodies and interferon-γ for cross-protection against influenza

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iScience


. 2021 Sep 15;24(10):103131.
doi: 10.1016/j.isci.2021.103131. eCollection 2021 Oct 22.
Synergistic effect of non-neutralizing antibodies and interferon-γ for cross-protection against influenza


Meito Shibuya ^{1 2 3} , Shigeyuki Tamiya ^{1 2 3} , Atsushi Kawai ^{1 2 3} , Toshiro Hirai ^{1 2 3} , Mark S Cragg ⁴ , Yasuo Yoshioka ^{1 2 3 5 6}



Affiliations

• PMID: 34622175
• PMCID: PMC8482522
• DOI: 10.1016/j.isci.2021.103131

Abstract

Current influenza vaccines do not typically confer cross-protection against antigenically mismatched strains. To develop vaccines conferring broader cross-protection, recent evidence indicates the crucial role of both cross-reactive antibodies and viral-specific CD4⁺ T cells; however, the precise mechanism of cross-protection is unclear. Furthermore, adjuvants that can efficiently induce cross-protective CD4⁺ T cells have not been identified. Here we show that CpG oligodeoxynucleotides combined with aluminum salts work as adjuvants for influenza vaccine and confer strong cross-protection in mice. Both cross-reactive antibodies and viral-specific CD4⁺ T cells contributed to cross-protection synergistically, with each individually ineffective. Furthermore, we found that downregulated expression of Fcγ receptor IIb on alveolar macrophages due to IFN-γ secreted by viral-specific CD4⁺ T cells improves the activity of cross-reactive antibodies. Our findings inform the development of optimal adjuvants for vaccines and how influenza vaccines confer broader cross-protection.

Keywords: Biological sciences; Immune response; Immunology.