GEM-PA-Based Subunit Vaccines of Crimean Congo Hemorrhagic Fever Induces Systemic Immune Responses in Mice

文献类型： 外文期刊

第一作者： Wang, Qi

作者： Wang, Qi;Xia, Xianzhu;Wang, Qi;Wang, Shen;Shi, Zhikang;Li, Zhengrong;Zhao, Yongkun;Feng, Na;Bi, Jinhao;Li, Entao;Wang, Tiecheng;Yan, Feihu;Yang, Songtao;Xia, Xianzhu;Shi, Zhikang;Bi, Jinhao;Wang, Jianzhong;Li, Zhengrong;Jiao, Cuicui;Jin, Hongli;Huang, Pei

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关键词： CCHFV; G-GP; subunit vaccine candidates; specific humoral and cellular responses; neutralizing antibody

期刊名称：VIRUSES-BASEL （ 影响因子：5.818； 五年影响因子：5.811 ）

ISSN：

年卷期： 2022 年 14 卷 8 期

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收录情况： SCI

摘要： The Crimean Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne bunyavirus of the Narovirus genus, which is the causative agent of Crimean Congo Hemorrhagic Fever (CCHF). CCHF is endemic in Africa, the Middle East, Eastern Europe and Asia, with a high case-fatality rate of up to 50% in humans. Currently, there are no approved vaccines or effective therapies available for CCHF. The GEM-PA is a safe, versatile and effective carrier system, which offers a cost-efficient, high-throughput platform for recovery and purification of subunit proteins for vaccines. In the present study, based on a GEM-PA surface display system, a GEM-PA based vaccine expressing three subunit vaccine candidates (G-GP, including G-eG(N), G-eG(C) and G-NAb) of CCHFV was developed, displaying the ectodomains of the structural glycoproteins eG(N), eG(C) and NAb, respectively. According to the immunological assays including indirect-ELISA, a micro-neutralization test of pseudo-virus and ELISpot, 5 mu g GPBLP(3) combined with Montanide ISA 201VG plus Poly (I:C) adjuvant (A-G-GP-5 mu g) elicited GP-specific humoral and cellular immunity in BALB/c mice after three vaccinations via subcutaneous injection (s.c.). The consistent data between IgG subtype and cytokine detection, ELISpot and cytokine detection indicated balanced Th1 and Th2 responses, of which G-eG(N) vaccines could elicit a stronger T-cell response post-vaccination, respectively. Moreover, all three vaccine candidates elicited high TNF-alpha, IL-6, and IL-10 cytokine levels in the supernatant of stimulated splenocytes in vitro. However, the neutralizing antibody (nAb) was only detected in A-G-eG(C) and A-G-eG(C) vaccination groups with the highest neutralizing titer of 128, suggesting that G-eG(C) could elicit a stronger humoral immune response. In conclusion, the GEM-PA surface display system could provide an efficient and convenient purification method for CCHFV subunit antigens, and the G-GP subunit vaccine candidates will be promising against CCHFV infections with excellent immunogenicity.

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