Synergistic effect of non-neutralizing antibodies and interferon-gamma for cross-protection against influenza
Synergistic effect of non-neutralizing antibodies and interferon-gamma for cross-protection against influenza
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.
103131
Shibuya, Meito
ac7a2d5e-50b2-4bf3-894c-54fed604ae07
Tamiya, Shigeyuki
cf3bcbff-22cc-4299-a4b8-1547a4133d84
Kawai, Atsushi
4fa3b5b4-05e5-4fce-9c11-19dc80186d61
Hirai, Toshiro
b33efe21-4ccc-4cfd-a0e1-aa98a2034a8b
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Yoshioka, Yasuno
eab10ee5-0fb4-451f-b256-1a2639270d56
22 October 2021
Shibuya, Meito
ac7a2d5e-50b2-4bf3-894c-54fed604ae07
Tamiya, Shigeyuki
cf3bcbff-22cc-4299-a4b8-1547a4133d84
Kawai, Atsushi
4fa3b5b4-05e5-4fce-9c11-19dc80186d61
Hirai, Toshiro
b33efe21-4ccc-4cfd-a0e1-aa98a2034a8b
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Yoshioka, Yasuno
eab10ee5-0fb4-451f-b256-1a2639270d56
Shibuya, Meito, Tamiya, Shigeyuki, Kawai, Atsushi, Hirai, Toshiro, Cragg, Mark and Yoshioka, Yasuno
(2021)
Synergistic effect of non-neutralizing antibodies and interferon-gamma for cross-protection against influenza.
iScience, 24 (10), , [103131].
(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.
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5. Revised-Supplemental Figure-Shibuya et al.
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3. Revised-Manuscript-Shibuya et al
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5. Graphical Abstract
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Accepted/In Press date: 22 August 2021
e-pub ahead of print date: 15 September 2021
Published date: 22 October 2021
Additional Information:
© 2021 The Author(s).
Identifiers
Local EPrints ID: 452239
URI: http://eprints.soton.ac.uk/id/eprint/452239
ISSN: 2589-0042
PURE UUID: ab23f54f-c383-4477-9d85-f306ff78aa62
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Date deposited: 01 Dec 2021 17:32
Last modified: 17 Mar 2024 02:46
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Author:
Meito Shibuya
Author:
Shigeyuki Tamiya
Author:
Atsushi Kawai
Author:
Toshiro Hirai
Author:
Yasuno Yoshioka
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