由于肾综合征出血热(HFRS)在全球范围内复发,更多的注意力集中在这种危险的疾病上。在中国和韩国,唯一可用的疫苗是针对汉坦病毒(HTNV)或首尔病毒(SEOV)的病毒灭活疫苗,但是这些疫苗的功效和安全性不足。因此,重要的是要开发更安全,更有效的新疫苗,以中和和调节HFRS患病率高的地区。我们采用生物信息学方法基于HTNV和SEOV膜中蛋白质共有序列的保守区域设计了重组蛋白质疫苗。S2果蝇表达系统用于增强蛋白质表达,溶解性和免疫原性。HTNV和SEOV的Gn和Gc蛋白成功表达后,小鼠免疫,和体液免疫,细胞免疫,在小鼠模型中系统评估了HFRS通用亚单位疫苗的体内保护作用。这些结果表明HFRS亚单位疫苗产生的结合和中和抗体水平升高,特别是IgG1,与传统的灭活HFRS疫苗相比。此外,免疫小鼠的脾细胞有效分泌IFN-r和IL-4细胞因子。此外,HTNV-Gc蛋白疫苗成功保护乳鼠免受HTNV感染并刺激GC反应。在这项研究中,研究了一种新的科学方法来开发一种通用的HFRS亚单位蛋白疫苗,该疫苗能够在小鼠中产生有效的体液和细胞免疫。结果表明,该疫苗可能是预防人类HFRS的有希望的候选疫苗。
Due to the global resurgence of hemorrhagic fever with renal syndrome (HFRS), more attention is being focused on this dangerous illness. In China and Korea, the only vaccines available are the virus-inactivated vaccine against Hantaan virus (
HTNV) or Seoul virus (SEOV), but their efficacy and safety are inadequate. Therefore, it is important to develop new vaccines that are safer and more efficient to neutralize and regulate areas with a high prevalence of HFRS. We employed bioinformatics methods to design a recombinant protein vaccine based on conserved regions of protein consensus sequences in
HTNV and SEOV membranes. The S2 Drosophila expression system was utilized to enhance protein expression, solubility and immunogenicity. After the Gn and Gc proteins of
HTNV and SEOV were successfully expressed, mice were immunized, and the humoral immunity, cellular immunity, and in vivo protection of the HFRS universal subunit vaccine were systematically evaluated in mouse models. These results indicated that the HFRS subunit vaccine generated elevated levels of binding and neutralizing antibodies, particularly IgG1, compared to that of the traditional inactivated HFRS vaccine. Additionally, the spleen cells of immunized mice secreted IFN-r and IL-4 cytokines effectively. Moreover, the
HTNV-Gc protein vaccine successfully protected suckling mice from
HTNV infection and stimulated GC responses. In this research, a new scientific approach is investigated to develop a universal HFRS subunit protein vaccine that is capable of producing effective humoral and cellular immunity in mice. The results suggest that this vaccine could be a promising candidate for preventing HFRS in humans.