Abstract

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by the orthohantaviruses Puumala, Dobrava-Belgrad (four genotypes), Hantaan (genotype Amur), and Seoul. In the Russian Federation, HFRS occupies the leading place among all natural focal human diseases. Formaldehyde, β-propiolactone, and ultraviolet radiation were tested to select the optimal method for viral inactivation during the development of a whole-virion vaccine against HFRS. The specific activity and the immunogenicity of the vaccine were determined, respectively, by the number of copies of viral RNA per 1 mL and by the neutralizing antibodies in the blood sera of BALB/c mice in response to immunization. Analysis of the immunogenicity of vaccines inactivated with formaldehyde, β-propiolactone, or UV radiation did not find significant differences in the level of induced neutralizing antibodies. At the same time, β-propiolactone has obvious technological advantages as compared to formaldehyde and UV radiation: the time of viral inactivation is reduced by dozens of times; neutralization of the inactivator and control of its content in the final vaccine are not required; and the amount of inappropriate protein in the vaccine is decreased due to the decrease in protein aggregation.

中文翻译：

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病毒灭活剂对汉坦病毒疫苗对肾综合征出血热的免疫原性的影响

摘要

肾综合征出血热（HFRS）是由正汉坦病毒Puumala，Dobrava-Belgrad（四种基因型），Hantaan（阿穆尔基因型）和首尔引起的一种急性人畜共患病。在俄罗斯联邦，HFRS在所有自然疫源性人类疾病中占据领先地位。测试了甲醛，β-丙内酯和紫外线辐射，从而在开发针对HFRS的全病毒疫苗过程中选择了最佳的病毒灭活方法。疫苗的比活性和免疫原性分别通过每1 mL病毒RNA的拷贝数和BALB / c小鼠血液中响应免疫的中和抗体来确定。用甲醛，β-丙内酯灭活的疫苗的免疫原性分析 或紫外线辐射在诱导的中和抗体水平上没有发现显着差异。同时，与甲醛和紫外线辐射相比，β-丙内酯具有明显的技术优势：病毒灭活的时间减少了数十倍；不需要中和灭活剂并控制其在最终疫苗中的含量；由于蛋白质聚集的减少，减少了疫苗中不适当蛋白质的数量。