An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed. Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test. The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo. This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.

中文翻译：

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在 HLA-A2.1/Kb 转基因小鼠中使用设计的线性多表位肽免疫诱导的针对汉坦病毒感染的保护性 CD8+ T 细胞反应

预防由汉坦病毒引起的疾病的有效疫苗是全球公共卫生的重点，但到目前为止，还没有疫苗被批准在全球范围内使用。因此，迫切需要具有高预防功效的新型疫苗。在此，我们设计合成了由 HLA-A*02 限制性 HTNV 细胞毒性 T 细胞 (CTL) 表位和泛 HLA-DR 结合表位 (PADRE) 组成的汉坦病毒 (HTNV) 线性多表位肽，并评估其免疫原性，多表位肽在 HLA-A2.1/Kb 转基因小鼠中的有效性以及干扰素 (IFN)-γ 酶联免疫斑点试验、细胞毒性介质检测、增殖试验和 HTNV 挑战试验。结果表明，特异性 IFN-γ 分泌 CTL 的频率高得多，颗粒酶 B 的产生水平高，多表位肽免疫小鼠的脾细胞中特异性CTLs增殖能力强于单一CTL表位。此外，多表位肽的预免疫可以降低小鼠肝脏、脾脏和肾脏中HTNV RNA负荷水平，表明多表位肽诱导的特异性CTL反应可以降低体内HTNV RNA负荷。该研究可为开发用于预防HTNV的新型肽疫苗提供重要基础。表明多表位肽诱导的特异性 CTL 反应可以减少体内 HTNV RNA 负载。该研究可为开发用于预防HTNV的新型肽疫苗提供重要基础。表明多表位肽诱导的特异性 CTL 反应可以减少体内 HTNV RNA 负荷。该研究可为开发用于预防HTNV的新型肽疫苗提供重要基础。