Enhancing Immune Response and Heterosubtypic Protection Ability of Inactivated H7N9 Vaccine by Using STING Agonist as a Mucosal Adjuvant.

Jian Luo,Xu-Ping Liu,Fei-Xia Gao,Min Zhang,Ze Chen,Ying-Lei Yi,Wen-Song Tan,Fei-Fei Xiong

doi:10.3389/fimmu.2019.02274

Jian Luo, Xu-Ping Liu + Show 6 more

Open Access

https://doi.org/10.3389/fimmu.2019.02274

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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.

Highlights

In March 2013, the first identified case of human infection with avian influenza A (H7N9) virus occurred in China, and as of 5 September 2018, a total of 1,567 human infections with H7N9 viruses, including at least 623 deaths, were reported during the fifth epidemic wave [1, 2]
Published clinical data demonstrated that H7N9 vaccines show poor immunogenicity in humans and using of novel adjuvants, such as MF59, AS03, immuno-stimulating complex (ISCOM), and aluminum hydroxide may have an important effect on improving vaccine immunogenicity for the uniquely low immunogenicity of this strain [6,7,8,9]
Previous studies have confirmed that the immunogenicity of H7N9 virus is relatively low in humans, and the usage of many different types of novel adjuvants may be necessary to improve the immunogenicity of H7N9 vaccines [9, 23, 24]

Summary

Introduction

In March 2013, the first identified case of human infection with avian influenza A (H7N9) virus occurred in China, and as of 5 September 2018, a total of 1,567 human infections with H7N9 viruses, including at least 623 deaths, were reported during the fifth epidemic wave [1, 2]. Some novel biological features of the H7N9 virus, such as the high frequency of drugresistance, emergence of highly pathogenic outbreaks in chickens and humans were discovered in this recent fifth epidemic wave in 2017 [2,3,4]. Published clinical data demonstrated that H7N9 vaccines show poor immunogenicity in humans and using of novel adjuvants, such as MF59, AS03, immuno-stimulating complex (ISCOM), and aluminum hydroxide may have an important effect on improving vaccine immunogenicity for the uniquely low immunogenicity of this strain [6,7,8,9]

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