包头医学院公共卫生学院;传染病溯源预警与智能决策全国重点实验室中国疾病预防控制中心病毒病预防控制所国家卫生健康委员会生物安全重点实验室;
痘苗病毒（Vaccinia virus,VACV）广泛用于疫苗与重组病毒载体。国内拥有自主知识产权的复制缺陷型痘苗病毒天坛株（Non-replicating Tiantan strain Vaccinia virus,NTV）作为新型猴痘疫苗近期已获得临床试验批准。前期研究中，本课题组通过回插基因C7L获得了重组病毒NTV-C7L(J)，然而该重组病毒的免疫原性未得到明显改善，迫切需要进一步改进。本研究利用同源重组技术对NTV-C7L(J)进行了二次基因改造，构建了缺失F1L基因的重组病毒NTV-ΔF1L-C7L(J)。BALB/c小鼠免疫结果表明，105 PFU免疫剂量二次肌肉注射，NTV-ΔF1L-C7L(J)可诱导出较强体液免疫反应和CD8+T细胞反应，其水平明显高于NTV与NTV-C7L(J)免疫组。与2×105 PFU剂量复制型痘苗病毒天坛株（Vaccinia virus Tiantan strain,VTT）组尾部划痕单剂免疫组相比，NTV-ΔF1L-C7L(J)抗体应答低但细胞免疫反应强。初次免疫后第42d采用致死剂量（107 PFU）VACV WR株进行小鼠滴鼻攻毒，NTV-ΔF1L-C7L(J)加强免疫组与VTT单剂免疫组均可提供完全保护，且攻毒后前者小鼠体重保护明显优于后者；但NTV与NTV-C7L(J)免疫组仅呈现部分保护（分别为60%和90%）。研究结果表明∶F1L基因的缺失明显提高了NTV及NTV-C7L(J)的免疫原性与免疫保护效果，且安全性优于VTT。本研究为开发新型痘苗病毒载体及更加安全高效阻断猴痘的疫苗提供了新思路和实验依据。
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.240322
中图分类号:R392
引用信息:
[1]刘士元,任皎,赵莉等.缺失F1L对重组复制缺陷痘苗病毒天坛株在小鼠中免疫原性与免疫保护效果的影响[J].病毒学报,2025,41(02):334-343.DOI:10.13242/j.cnki.bingduxuebao.240322.
基金信息:
国家重点研发计划（项目号∶2022YFC2304100）,题目∶新冠与流感等大流行风险病原体多肽疫苗的研制; 国家自然科学基金（项目号∶82241066）,题目∶猴痘病毒和痘苗病毒颗粒的高分辨率原位结构及其生物学功能研究~~