将大肠杆菌热不稳定肠毒素B亚基掺入狂犬病毒颗粒中,增强了狂犬病毒在小鼠和犬体内的免疫原性

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Biosafety and Health Pub Date : 2023-10-01 DOI:10.1016/j.bsheal.2023.05.005
Zhiyuan Gong , Hailun Li , Meichen Qian , Yujie Bai , Hongli Jin , Jingxuan Sun , Mengyao Zhang , Cuicui Jiao , Pei Huang , Yuanyuan Li , Haili Zhang , Hualei Wang
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引用次数: 0

摘要

尽管狂犬病灭活疫苗具有高安全性的优点,但对狂犬病病毒(RABV)感染的有效保护通常需要多次、高剂量的免疫接种。在病毒颗粒中加入分子佐剂已被发现是提高灭活疫苗免疫效力的有用策略。在本研究中,我们构建了一种重组病毒rCVS11-LTB,该病毒在RABV颗粒表面嵌合表达分子佐剂热不稳定肠毒素B亚基(LTB)蛋白。发现rCVS11-LTB通过激活树突状细胞(DC)来促进体内免疫原性。我们的结果表明,与亲本病毒rCVS11相比,灭活的rCVS11-LTB能够在小鼠和狗中诱导更高水平的病毒中和抗体(VNA),以增强小鼠的细胞免疫反应和T细胞免疫记忆,并且还能够在小鼠中提供100%的保护,使其免受狂犬病病毒的致命剂量,表明其作为安全有效的狂犬病灭活候选疫苗的潜力。
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Incorporation of Escherichia coli heat-labile enterotoxin B subunit into rabies virus particles enhances its immunogenicity in mice and dogs

Although inactivated vaccines against rabies have the advantage of high safety, effective protection against rabies virus (RABV) infection often requires multiple, high-dose immunization. Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines. In this study, we constructed a recombinant virus, rCVS11-LTB, which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit (LTB) protein on the surface of the RABV particles. Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells (DCs). Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs than the parent virus rCVS11, to enhance the cellular immune response and T cell immune memory in mice, and was also able to provide 100% protection in mice from lethal doses of rabies virus, indicating its potential as a safe and effective inactivated rabies vaccine candidate.

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来源期刊
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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