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Front Immunol. 2019 Sep 27;10:2274. doi: 10.3389/fimmu.2019.02274. eCollection 2019. Enhancing Immune Response and Heterosubtypic Protection Ability of Inactivated H7N9 Vaccine by Using STING Agonist as a Mucosal Adjuvant.
Luo J1,2, Liu XP1, Xiong FF2, Gao FX2, Yi YL2, Zhang M2, Chen Z2, Tan WS1.
Author information
1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China. 2 Shanghai Institute of Biological Products, Shanghai, China.
Abstract
Influenza vaccines for H7N9 subtype have shown low immunogenicity in human clinical trials. Using novel adjuvants might represent the optimal available option in vaccine development. In this study, we demonstrated that the using of the STING agonist cGAMP as a mucosal adjuvant is effective in enhancing humoral, cellular and mucosal immune responses of whole virus, inactivated H7N9 vaccine in mice. A single dose of immunization was able to completely protect mice against a high lethal doses of homologous virus challenge with an significant dose-sparing effect. We also found that intranasal co-administration of H7N9 vaccine with cGAMP could provide effective cross protection against H1N1, H3N2, and H9N2 influenza virus. Furthermore, cGAMP induced significantly higher nucleoprotein specific CD4+ and CD8+ T cells responses in immunized mice, as well as upregulated the IFN-γ and Granzyme B expression in the lung tissue of mice in the early stages post a heterosubtypic virus challenge. These results indicated that STING agonist cGAMP was expected to be an effective mucosal immune adjuvant for pre-pandemic vaccines such as H7N9 vaccines, and the cGAMP combined nasal inactivated influenza vaccine will also be a promising strategy for development of broad-spectrum influenza vaccines.
Copyright ? 2019 Luo, Liu, Xiong, Gao, Yi, Zhang, Chen and Tan.
KEYWORDS:
H7N9; STING; cross protection; mucosal adjuvant; whole viron vaccine
PMID: 31611875 PMCID: PMC6777483 DOI: 10.3389/fimmu.2019.02274