BACKGROUND Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimens priming with vaccines and boosting with recombinant adenovirus vaccines have been proven to be successful strategies for protecting against viruses in experimental animal models. METHODS In this study, heterologous and homologous prime-boost strategies using an attenuated salmonella vaccine and a recombinant adenovirus vaccine expressing prM-E or the E gene of TMUV were evaluated to protect ducks against TMUV infection for the first time, including priming and boosting with the attenuated salmonella vaccine, priming and boosting with the recombinant adenovirus vaccine, and priming with the attenuated salmonella vaccine and boosting with the recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for clinical symptoms, mortality, viral loads and histopathological lesions after these different strategies. RESULTS Compared with the homologous prime-boost strategies, the heterologous prime-boost regimen produced higher levels of neutralizing antibodies and IgG antibodies against TMUV. Additionally, it could induce higher levels of IFN-γ than homologous prime-boost strategies in the later stage. Interestingly, the heterologous prime-boost strategy induced higher levels of IL-4 in the early stage, but the IL-4 levels gradually decreased and were even lower than those induced by the homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks, with low viral titres, no clinical symptoms and histopathological lesions in this experiment after challenge with TMUV, while slight clinical symptoms and histopathological lesions were observed with the homologous prime-boost strategies. CONCLUSIONS Our results indicated that the heterologous prime-boost strategy induced higher levels of humoral and cellular immune responses and better protection against TMUV infection in ducks than the homologous prime-boost strategies, suggesting that the heterologous prime-boost strategy is an important candidate for the design of a novel vaccine strategy against TMUV.

中文翻译：

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异源初免-加强：针对天布苏病毒的重要候选免疫策略。


背景技术天布苏病毒(TMUV)是一种新出现的致病性黄病毒，在鸭群之间迅速传播，给我国养鸭业造成巨大的经济损失。疫苗接种是预防 TMUV 最有效的方法。因此，寻找针对TMUV的有效疫苗策略刻不容缓。已证明，用疫苗引发和用重组腺病毒疫苗加强的异源初免-加强方案是在实验动物模型中预防病毒的成功策略。方法在这项研究中，首次评估了使用减毒沙门氏菌疫苗和表达 prM-E 或 TMUV E 基因的重组腺病毒疫苗的异源和同源初免-加强策略，以保护鸭子免受 TMUV 感染，包括用减毒沙门氏菌疫苗、重组腺病毒疫苗初免和加强、以及减毒沙门氏菌疫苗初免和重组腺病毒疫苗加强。检测并评估体液和细胞免疫反应。然后，我们在加强后 12 天用 TMUV 挑战鸭子，以在这些不同的策略后检测临床症状、死亡率、病毒载量和组织病理学病变。结果 与同源初免-加强策略相比，异源初免-加强方案产生了更高水平的抗 TMUV 中和抗体和 IgG 抗体。此外，它可以在后期诱导比同源初免-加强策略更高水平的 IFN-γ。 有趣的是，异源初免-加强策略在早期诱导较高水平的IL-4，但后期IL-4水平逐渐下降，甚至低于同源初免-加强策略诱导的IL-4水平。此外，异源初免-加强策略可以有效保护鸭子，本实验中TMUV攻击后病毒滴度低，无临床症状和组织病理学病变，而同源初免-加强策略则观察到轻微的临床症状和组织病理学病变。结论 我们的结果表明，与同源初免-加强策略相比，异源初免-加强策略在鸭中诱导更高水平的体液和细胞免疫反应，并更好地防止 TMUV 感染，这表明异源初免-加强策略是鸭的重要候选策略。设计针对 TMUV 的新型疫苗策略。