Immunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models
Immunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models
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DOI：
10.1093/infdis/jiy187
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发表时间：
2018-08-01
影响因子：
6.4
通讯作者：
Chen, Wei
中科院分区：
文献类型：
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作者：
Guo, Qiang;Chan, Jasper Fuk-Woo;Chen, Wei
背景寨卡病毒（ZIKV）感染可能与严重并发症有关，并通过媒介传播和非媒介传播途径传播。腺病毒载体疫苗代表了ZIKV流行病的有利控制措施，因为它们已被证明是安全的，免疫原性的，并且可快速产生用于其他新出现的病毒感染。使用非致死动物模型和/或非流行性ZIKV毒株进行2种先前报道的腺病毒载体ZIKV疫苗的评估。我们构建了两种新型的人腺病毒5（Ad 5）载体疫苗，分别含有ZIKV前膜包膜（Ad 5-Sig-prM-Env）和包膜（Ad 5-Env）蛋白，并使用流行性ZIKV毒株在多种非致死和致死动物模型中对其进行了评估。两种疫苗在免疫活性BALB/c小鼠中均引起了强烈的体液和细胞免疫应答。地塞米松免疫抑制小鼠接种任一种疫苗均表现出稳健和持久的抗体应答，血液和组织病毒载量显著低于对照组（P <0.05）。在干扰素α/β受体缺陷的A129小鼠中也观察到类似的结果。在这两种免疫受损的动物模型中，与Ad 5-Env接种的小鼠相比，Ad 5-Sig-prM-Env接种的小鼠具有显著（P <0.05）更高的抗ZIKV特异性中和抗体滴度和更低的（不可检测的）病毒载量。中和抗体滴度与病毒载量之间的密切相关有助于解释Ad 5-Sig-prM-Env比Ad 5-Env更好的保护效果。在Ad 5-Sig-prM-Env疫苗接种的A129小鼠中不存在回忆应答。Ad 5-Sig-prM-Env在小鼠中提供针对ZIKV感染的灭菌保护。
Background. Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain.Methods. We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains.Results. Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-alpha/beta receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice.Conclusions. Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.