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利用序贯免疫具有较高中和效价以及较低副反应效果的特性，探讨一种具有Wuhan株序列的小剂量S1蛋白编码mRNA疫苗和具有变异株突变特征的蛋白疫苗的序贯免疫策略。制备自主设计序列的mRNA和蛋白疫苗，经测序，转录表达及抗原鉴定后免疫小鼠，分别检测不同免疫策略诱导的中和抗体、抗S蛋白IgG抗体以及特异性T细胞增殖情况。实验用mRNA疫苗能够在293细胞中有效翻译且呈现明显的量效关系；具有多种变异株突变位点的蛋白疫苗能够为患者恢复期血清和抗S蛋白抗体所识别。两种疫苗组合经皮内和肌肉序贯免疫小鼠能够诱导较单剂免疫或同源加强策略更高的，包括中和抗体的抗体反应，其可以维持至加强免疫后的140d。另外，其诱导的血清能够识别不同变异株的S1蛋白。序贯免疫诱导的特异分泌IFN-γ T细胞增殖反应亦显示了类似的结果。mRNA/蛋白抗原组合疫苗进行序贯免疫的策略具有能够产生较高中和抗体、维持时间较长和易于针对不同变异株设计快速反应的优点，可以作为应对新冠变异株的候选疫苗策略。
Abstract：Based on the advantages of sequential immunization with high neutralizing antibody titer and low side effects, we explore the immunological characters of a sequential immunization strategy with low-dose mRNA vaccine of S1 protein of Wuhan strain and a protein vaccine with mutant characteristics of various variants.mRNA and protein vaccines with proprietary intellectual property rights were prepared. After identification of vaccine specificity, mice were immunized with these vaccines following special order. Neutralizing antibodies, anti-S protein IgG antibodies and specific T cell proliferation induced by different immunization strategies were detected respectively. The experimental mRNA vaccine could be effectively translated in 293 cells and showed an obvious dose-effect relationship. The protein vaccine with multiple mutant sites could be recognized by convalescent patients' serum and anti-S protein antibody. Sequential immunization of mice intradermally or intramuscularly with prime-boost by mRNA and protein vaccines was able to induce higher neutralizing antibody, anti-S protein IgG antibody than single-dose immunization or homologous boosting strategies, and maintained up to 140 days after boosting. In addition, the induced serum can recognize the S1 protein of different variants. Similar results were also shown in the responses of specific T cells secreting IFN-γ induced by sequential immunization. The strategy of sequential immunization with mRNA/protein antigen combination vaccine has the advantages of producing higher neutralizing antibody, maintaining a longer duration, and easy to design rapid responses against various variants. It can be used as a candidate vaccine strategy against new coronavirus variants.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004281
中图分类号:R392
引用信息:
[1]母昌勇,彭晓武,刘昌娥,等.一种应对新冠变异株疫苗研制的免疫策略研究[J].病毒学报,2023,39(02):322-333.DOI:10.13242/j.cnki.bingduxuebao.004281.
2022-04-02
2022
2022-08-05
2023-03-16
2023
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2023-03-20
2023-03-20
2023-03-20