Design of a multi-epitope vaccine candidate against Brucella melitensis.

Design of a multi-epitope vaccine candidate against Brucella melitensis.
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针对羊布鲁氏菌的多表位候选疫苗的设计

DOI:
10.1038/s41598-022-14427-z
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发表时间:
2022-06-16
期刊:
影响因子:
4.6
通讯作者:
Zhang, Fengbo
Zhang, Fengbo
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li, Min;Zhu, Yuejie;Niu, Ce;Xie, Xinru;Haimiti, Gulishati;Guo, Wenhong;Yu, Mingkai;Chen, Zhiqiang;Ding, Jianbing;Zhang, Fengbo

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布鲁氏菌是一种典型的兼性胞内细菌,可引起人畜共患感染。对于布鲁氏菌,目前的医疗手段很难消除。因此,应该设计一种多表位疫苗(MEV)来预防布鲁氏菌感染。为此,我们采用了来自Omp10、Omp25、Omp31和BtpB的反向疫苗学方法。最后,我们获得了13个细胞毒性T淋巴细胞(CTL)表位,17个辅助T淋巴细胞(HTL)表位,9个线性B细胞表位和2个构象B细胞表位。为了保持蛋白正常折叠,我们将AAY、GPGPG和KK分别连接到CTL表位、HTL表位和B细胞表位上。在疫苗肽的n端添加适当的佐剂以增强免疫原性。为了评价其免疫原性、稳定性、安全性和可行性,通过连接物和佐剂构建了含有806个氨基酸的MEV。此外,通过分子对接和分子动力学模拟验证了MEV-TLR4的亲和性和稳定性。然后,进行了密码子适应性和硅克隆研究,以确定表达MEV的可能密码子。动物实验结果表明,MEV具有较高的免疫原性。本研究为布鲁氏菌疫苗的研制提供了理论基础。
Brucella is a typical facultative intracellular bacterium that can cause zoonotic infections. For Brucella, it is difficult to eliminate with current medical treatment. Therefore, a multi-epitope vaccine (MEV) should be designed to prevent Brucella infection. For this purpose, we applied the reverse vaccinology approach from Omp10, Omp25, Omp31 and BtpB. Finally, we obtained 13 cytotoxic T lymphocyte (CTL) epitopes, 17 helper T lymphocyte (HTL) epitopes, 9 linear B cell epitopes, and 2 conformational B cell epitopes for further study. To keep the protein folded normally, we linked AAY, GPGPG, and KK to CTL epitopes, HTL epitopes, and B cell epitopes, respectively. The N-terminal of the vaccine peptide is supplemented with appropriate adjuvants to enhance immunogenicity. To evaluate its immunogenicity, stability, safety, and feasibility, a final MEV containing 806 amino acids was constructed by linking linkers and adjuvants. In addition, molecular docking and molecular dynamics simulations were performed to verify the affinity and stability of the MEV-TLR4. Then, codon adaptation and in silico cloning studies were carried out to identify the possible codons for expressing the MEV. In animal experiments, the results demonstrated that the MEV had high immunogenicity. Collectively, this study provided a theoretical basis for the development of a Brucella vaccine.
利用生物信息学方法设计基于T和B细胞表位的新型布鲁氏菌多表位疫苗
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