Lysosome-Associated Membrane Protein Targeting Strategy Improved Immunogenicity of Glycoprotein-Based DNA Vaccine for Marburg Virus

被引:1
|
作者
Zhang, Xiyang [1 ,2 ]
Sun, Yubo [1 ]
Zhang, Junqi [1 ]
Wei, Hengzheng [1 ]
Wang, Jing [1 ]
Hu, Chenchen [1 ]
Liu, Yang [3 ]
Cai, Sirui [1 ]
Yuan, Qinghong [1 ]
Wang, Yueyue [1 ]
Sun, Yuanjie [1 ]
Yang, Shuya [1 ]
Jiang, Dongbo [1 ]
Yang, Kun [1 ]
机构
[1] Air Force Med Univ, Mil Med Univ 4, Basic Med Sch, Dept Immunol,Key Lab Biohazard Damage & Prevent Me, Xian 710032, Peoples R China
[2] Air Force Med Univ, Mil Med Univ 4, Mil Med Innovat Ctr, Xian 710032, Peoples R China
[3] Shaanxi Prov Ctr Dis Control & Prevent, Inst AIDS Prevent & Control, Xian 710054, Peoples R China
基金
中国国家自然科学基金;
关键词
Marburg virus (MARV); DNA vaccine; lysosome-associated membrane protein (LAMP); Marburg hemorrhagic fever (MHF); TERM IMMUNE PROTECTION; RECOMBINANT; OUTBREAK;
D O I
10.3390/vaccines12091013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Marburg hemorrhagic fever (MHF) is a fatal infectious disease caused by Marburg virus (MARV) infection, and MARV has been identified as a priority pathogen for vaccine development by the WHO. The glycoprotein (GP) of MARV mediates viral adhesion and invasion of host cells and therefore can be used as an effective target for vaccine development. Moreover, DNA vaccines have unique advantages, such as simple construction processes, low production costs, and few adverse reactions, but their immunogenicity may decrease due to the poor absorption rate of plasmids. Lysosome-associated membrane protein 1 (LAMP1) can direct antigens to lysosomes and endosomes and has great potential for improving the immunogenicity of nucleic acid vaccines. Therefore, we constructed a DNA vaccine based on a codon-optimized MARV GP (ID MF939097.1) fused with LAMP1 and explored the effect of a LAMP targeting strategy on improving the immunogenicity of the MARV DNA vaccine. ELISA, ELISpot, and flow cytometry revealed that the introduction of LAMP1 into the MARV DNA candidate vaccine improved the humoral and cellular immune response, enhanced the secretion of cytokines, and established long-term immune protection. Transcriptome analysis revealed that the LAMP targeting strategy significantly enriched antigen processing and presentation-related pathways, especially the MHC class II-related pathway, in the candidate vaccine. Our study broadens the strategic vision for enhanced DNA vaccine design and provides a promising candidate vaccine for MHF prevention.
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页数:14
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