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目的 本研究旨在开发基于重组腺相关病毒（Recombinant adeno-associated virus, rAAV）载体的Ⅱ型单纯疱疹病毒（Herpes simplex virus type 2, HSV-2）gD表位疫苗。HSV-2感染导致生殖器疱疹，并终生潜伏于背根神经节，在机体免疫水平低下时复发，且目前尚无根治方法，是全球最严重的性传播疾病之一。目前尚无相关疫苗获批，现有治疗药物存在抗药性和毒副作用，因此，亟需开发有效预防HSV-2感染和传播的疫苗。方法 本研究通过抗原表位预测软件筛选HSV-2包膜蛋白gD的两个片段，通过基因重组及病毒包装构建了两个重组腺相关病毒rAAV-sn-9和rAAV-sn-10。在感染细胞系及小鼠后，均可分泌表达相应蛋白。以之作为病毒载体疫苗，在BALB/c小鼠HSV-2感染模型中评价其免疫保护效果。结果 rAAV载体疫苗在BALB/c小鼠模型中安全耐受，可有效诱导特异性体液免疫和细胞免疫。HSV-2攻毒试验进一步表明，rAAV载体疫苗可减缓感染小鼠体重下降、降低死亡率，并显著降低生殖道和背根神经节病毒载量。结论 本研究构建的rAAV载体疫苗对小鼠HSV-2感染具有免疫保护作用，为新型HSV-2疫苗开发提供了新的思路。
Abstract：Objective To construct a recombinant adeno-associated virus(rAAV)–based herpes simplex virus type 2(HSV-2) glycoprotein D(gD) epitope vaccine and to evaluate its immunogenicity and protective efficacy in a mouse model.Methods Two epitope fragments of HSV-2 envelope glycoprotein D were selected using antigen epitope prediction software. Recombinant AAV vectors expressing these epitopes, designated rAAV-sn-9 and rAAV-sn-10, were generated through gene recombination and viral packaging. Expression of the target proteins was verified in infected cell lines and in mice. BALB/c mice were immunized intramuscularly with the rAAV vectors, and HSV-2 – specific humoral and cellular immune responses were subsequently assessed.Protective efficacy was further evaluated using an HSV-2 challenge model.Results The rAAV-based vaccines were well tolerated in BALB/c mice and exhibited a favorable safety profile. Immunization induced robust HSV-2 – specific humoral and cellular immune responses. Following HSV-2 challenge, vaccinated mice showed attenuated body weight loss, reduced mortality, and significantly decreased viral loads in the genital tract and dorsal root ganglia compared with control groups.Conclusion The rAAV-based HSV-2 gD epitope vaccines provided effective immunoprotection against HSV-2 infection in mice, supporting their potential as a promising strategy for the development of novel HSV-2 vaccines.
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基本信息:
中图分类号:R392
引用信息:
[1]荆明箴,占雨欣,钟歌唱,等.基于重组腺相关病毒载体的HSV-2gD表位疫苗构建及小鼠免疫保护作用研究[J].病毒学报().
基金信息:
武汉市医学科学研究项目（项目号：WX23A40）,题目：乙肝核心抗原在基于AAV构建的小鼠慢性乙肝感染模型中的治疗作用研究
2026-02-09
2026-02-09
2026-02-09