实验性汉坦病毒疫苗成分中的碳水化合物佐剂对豚鼠血清中中和抗体动态的影响

S. Kurashova, M. Egorova, A. Vetrova, M. Balovneva, Yulia V. Popova, R. Teodorovich, Anna A. Mironenko, P. G. Aparin, V. L. Lvov, Eugeny A. Tkachenko, T. Dzagurova
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摘要

导言。疫苗接种可能是预防肾综合征出血热(HFRS)的最有效手段,肾综合征出血热是主要的人畜共患病之一,也是导致人类自然疾病的主要原因。因此,研究开发一种有效的疫苗,寻找能增强和延长免疫反应、降低抗原浓度和减少给药次数的无毒、有效的新型佐剂是一项紧迫的任务。本研究的目的是确定基于普马拉病毒(HV)的实验性汉坦病毒疫苗的免疫原活性对原形抗原剂量和与碳水化合物佐剂结合的抗原剂量的依赖性。材料和方法通过对豚鼠(Cavia porcellus)进行 3 次免疫(第 0、14、182 天)后诱导中和抗体,研究了作为 HV 一部分的 Ac3-LPS S. sonnei 和 S. flexneri 1B 以及纳米乳化角鲨烯 Sepivac SWE(SWE)乳剂在最佳和最小剂量下的免疫佐剂效应。通过在 Vero E6 细胞培养物中抑制 50%的病灶单位来评估 HV 在中和反应中的免疫原性差异。结果显示使用最佳剂量的 HV 及其与佐剂结合免疫后,中和抗体水平均有统计学意义上的显著提高。Ac3-LPS S. sonnei 和 SWE 的免疫佐剂效果最明显,浓度分别为 50 和 100 微克/剂量。汉坦病毒疫苗与 Ac3-LPS S. sonnei 和 SWE 的组合免疫佐剂效应有助于增强免疫反应及其持续时间。加入 SWE 后,抗原剂量减少了 10 倍,从而优化了疫苗的免疫反应。结论本研究结果表明,在疫苗中使用 Ac3-LPS S. sonnei 和 Sepivac SWE 有助于预防 HFRS。
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The effect of carbohydrate adjuvants in the composition of the experimental hantavirus vaccine on the dynamics of neutralizing antibodies in the blood sera of guinea pigs
Introduction. Vaccination could be the most effective means of preventing hemorrhagic fever with renal syndrome (HFRS), which is one of the leading zoonoses and a major cause of natural disease in humans. Therefore, research to develop an effective vaccine and the search for new non-toxic and effective adjuvants that can enhance and prolong the immune response, reduce the antigen concentration and reduce the frequency of dose administration is an urgent task. The aim of the study was to determine the dependence of the immunogenic activity of an experimental hantavirus vaccine based on Puumala virus (HV) on the antigen dose both in native form and in combination with carbohydrate adjuvants. Materials and methods. The immunoadjuvant effect of Ac3-LPS S. sonnei and S. flexneri 1B and emulsions of nanoemulsified squalene Sepivac SWE (SWE) as part of HV at the optimal and minimal doses was investigated by induction of neutralising antibodies after 3-fold immunisation (day 0, 14, 182) of guinea pigs (Cavia porcellus). Differences in the immunogenic activity of HV were assessed in the neutralisation reaction by 50% suppression of focal units in Vero E6 cell cultures. Results. A statistically significant increase in neutralising antibodies levels was observed after immunization both with HV at the optimal dose and for its combination with adjuvants. Ac3-LPS S. sonnei and SWE showed the most pronounced immunoadjuvant effect at concentrations of 50 and 100 μg/dose, respectively. The immunoadjuvant effect of the combination of the hantavirus vaccine with Ac3-LPS S. sonnei and SWE contributed to both an enhanced immune response and its duration. The tenfold reduction of the antigen dose in the presence of SWE allows optimization of the immune response to the vaccine. Conclusion. The results of this study show the prospects of using Ac3-LPS S. sonnei and Sepivac SWE in the vaccine for the prevention of HFRS.
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