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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02274

Enhancing immune response and heterosubtypic protection ability of inactivated H7N9 vaccine by using STING agonist as a mucosal adjuvant

 Jian Luo1, 2, Xu-ping Liu1, Fei-fei Xiong2, Fei-xia Gao2,  Ying-lei Yi2, Min Zhang2,  Ze Chen2* and Wen-song Tan1*
  • 1State Key Laboratory of Bioreactor Engineering,School of Biotechnology, East China University of Science and Technology, China
  • 2Shanghai Institute Of Biological Products, China

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 avian 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.

Keywords: H7N9, whole viron vaccine, STING, Mucosal adjuvant, Cross Protection

Received: 11 Jun 2019; Accepted: 09 Sep 2019.

Copyright: © 2019 Luo, Liu, Xiong, Gao, Yi, Zhang, Chen and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Ze Chen, Shanghai Institute Of Biological Products, Shanghai, 200052, Shanghai Municipality, China, chenze2005@hotmail.com
Mx. Wen-song Tan, State Key Laboratory of Bioreactor Engineering,School of Biotechnology, East China University of Science and Technology, Shanghai, China, wstan@ecust.edu.cn