Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Department of Microbiology, The Fourth Military Medical University, Xi'an, 710032, China.
Virol J. 2020 Oct 7;17(1):146. doi: 10.1186/s12985-020-01421-y.
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/K 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.
一种能够预防汉坦病毒引起的疾病的有效疫苗是全球公共卫生的当务之急，但迄今为止，还没有一种疫苗获得全球批准使用。因此，迫切需要具有高预防效果的新型疫苗。
在此，我们设计并合成了汉坦病毒（HTNV）线性多表位肽，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，并通过 IFN-γ 酶联免疫斑点试验、细胞毒性介质检测、增殖试验和 HTNV 挑战试验评估了多表位肽在 IFN-γ 酶联免疫斑点试验、细胞毒性介质检测、增殖试验和 HTNV 挑战试验中的免疫原性和有效性。
结果表明，与单一 CTL 表位相比，多表位肽免疫的小鼠脾细胞中特异性 IFN-γ 分泌 CTL 的频率更高，颗粒酶 B 产生水平更高，特异性 CTL 的增殖能力更强。此外，多表位肽的预免疫可以降低 HTNV RNA 在小鼠肝脏、脾脏和肾脏中的载量，表明多表位肽诱导的特异性 CTL 反应可以减少体内 HTNV RNA 的载量。
本研究可能为开发新型 HTNV 预防肽疫苗提供重要基础。
