Enhanced Immune Response Against Echinococcus Granulosus Through a CTLA-4/B7 Affinity-Based Vaccine

被引:0
作者
Zhu, Yuejie [1 ]
He, Yueyue [2 ]
Yin, Ziyue [2 ,3 ]
Chen, Na [4 ]
Qi, Xingxing [4 ]
Ding, Jianbing [2 ,5 ]
Li, Yujiao [6 ]
Zhang, Fengbo [4 ]
机构
[1] Xinjiang Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Urumqi 830054, Peoples R China
[2] Xinjiang Med Univ, Sch Basic Med Sci, Dept Immunol, Urumqi 830011, Peoples R China
[3] Guilin Med Univ, Sch Publ Hlth, Guilin 541100, Peoples R China
[4] Xinjiang Med Univ, Affiliated Hosp 1, Clin Lab Ctr, Urumqi 830054, Peoples R China
[5] Xinjiang Med Univ, Affiliated Hosp 1, State Key Lab Pathogenesis Prevent Treatment Cent, Urumqi 830054, Peoples R China
[6] Xinjiang Med Univ, Affiliated Hosp 1, Postdoctoral Res Stn Clin Med, Urumqi 830054, Peoples R China
基金
中国国家自然科学基金;
关键词
CE; vaccine; epitope; immunoinformatics; CTLA-4; molecular docking; CELL EPITOPES; ANTIGEN; PREDICTION; MANAGEMENT; DISCOVERY; DIAGNOSIS; PROTEINS;
D O I
10.3390/vaccines12121440
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Echinococcosis is a zoonotic infectious disease that poses a significant threat to the health of individuals living in rural regions. While vaccination represents a potential strategy for disease prevention, there is currently no effective vaccine available for humans to prevent cystic echinococcosis (CE). This study aimed to design a novel multi-epitope vaccine (MEV) against Echinococcus granulosus for human use, employing immunoinformatics methods. Methods: We identified core epitopes from two key antigens, EgA31 and EgG1Y162, and integrated them into the immunoglobulin variable region of CTLA-4 (CTLA-4lgV) to create the CVE31-162 vaccine construct. The secondary and tertiary structures of the CVE31-162 were established using bioinformatics methods. The interaction between the CVE31-162 and B7 molecules was assessed through molecular dynamics simulations. Finally, both in vitro and in vivo experiments were conducted to validate the effectiveness of the CVE31-162 against the immunological effects of Echinococcus granulosus. Results: Bioinformatics analysis indicated that CVE31-162 exhibits favorable antigenicity, stability, and non-allergenicity. Furthermore, CVE31-162 demonstrated a stable three-dimensional structural model. Molecular docking (MD) and molecular dynamics simulations (MDS) revealed a strong binding affinity between CVE31-162 and B7 molecules. Immune simulation results suggested that the vaccine elicits robust humoral and cell-mediated immune responses. Both in vitro and in vivo experiments demonstrated that immunized mice exhibited significantly elevated levels of antigen-specific antibodies and enhanced lymphocyte proliferation compared to the control group. Conclusions: CVE31-162, which is based on the interaction between CTLA-4 and B7, represents a promising multi-epitope vaccine for Echinococcus granulosus.
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页数:21
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