Vaccine candidate designed against carcinoembryonic antigen-related cell adhesion molecules using immunoinformatics tools.

Vaccine candidate designed against carcinoembryonic antigen-related cell adhesion molecules using immunoinformatics tools.
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DOI:
10.1080/07391102.2020.1797539
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发表时间:
2021-10
影响因子:
4.4
通讯作者:
Cui F
Cui F
中科院分区:
生物学3区
文献类型:
--
作者:
Gupta A;Rosato AJ;Cui F

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癌胚抗原相关细胞粘附 (CEACAM) 分子属于膜糖蛋白家族,介导细胞间相互作用,影响细胞生长、免疫细胞激活、细胞凋亡和肿瘤抑制。几个家族成员(CEACAM1、CEACAM5 和 CEACAM6)在癌症中高表达,并且它们共享一个保守的 N 末端结构域,可作为癌症免疫治疗的有吸引力的靶标。使用免疫信息学工具开发了针对该保守结构域的多表位候选疫苗。具体来说,预测与 MHC I 类和 II 类分子相互作用的几个表位通过适当的接头连接在一起。疫苗的三级结构是通过同源性和从头建模生成的。表位与 MHC 结构的分子对接表明,最低能量构象是与 MHC 分子的抗原结合沟结合的表位。随后的分子动力学模拟证实了溶液中结合构象的稳定性。预测的疫苗具有相对较高的抗原性和较低的致敏性,表明它是进一步完善和开发的理想候选疫苗。
Carcinoembryonic antigen-related cell adhesion (CEACAM) molecules belong to a family of membrane glycoproteins that mediate intercellular interactions influencing cellular growth, immune cell activation, apoptosis, and tumor suppression. Several family members (CEACAM1, CEACAM5, and CEACAM6) are highly expressed in cancers, and they share a conserved N-terminal domain that serves as an attractive target for cancer immunotherapy. A multi-epitope vaccine candidate against this conserved domain has been developed using immunoinformatics tools. Specifically, several epitopes predicted to interact with MHC class I and II molecules were linked together with appropriate linkers. The tertiary structure of the vaccine is generated by homology and ab initio modeling. Molecular docking of epitopes to MHC structures has revealed that the lowest energy conformations are the epitopes bound to the antigen-binding groove of the MHC molecules. Subsequent molecular dynamics simulation has confirmed the stability of the binding conformations in solution. The predicted vaccine has relatively high antigenicity and low allergenicity, suggesting that it is an ideal candidate for further refinement and development.
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