Conjugation of beta-Glucan with the Hydrazone and Disulfide Linkers Markedly Improves the Immunogenicity of Zika Virus E Protein
文献类型：期刊论文
| 作者 | Qi, Jinming1; Yin, Ying2; Yu, Weili1; Shen, Lijuan1; Xu, Junjie2; Hu, Tao1 |
| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2020-06-01 |
| 卷号 | 17期号:6页码:1933-1944 |
| 关键词 | Zika virus beta-glucan E protein adjuvant hydrazine disulfide |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.0c00010 |
| 英文摘要 | The diseases caused by Zika virus (ZIKV) have received widespread concerns. As a key viral element of ZIKV, E protein was an ideal antigen for vaccine development. However, the poor immunogenicity of E protein necessitated the formulation with adjuvants. Formulation of E protein by conjugation with beta-glucan was a strategy to improve the immunogenicity of E protein, where beta-glucan was a polysaccharide adjuvant that could activate macrophages and trigger intracellular processes. However, the antigenic epitopes of E protein and the immunomodulatory sites of beta-glucan were shielded in the conjugate. Moreover, the conjugate might elicit the undesired immune response to beta-glucan. Thus, the acidic-labile hydrazone and the thiol-sensitive disulfide bonds were used as the linkers between E protein and beta-glucan. Hydrazone hydrolysis and disulfide reduction could sufficiently detach the two components in the immune cells to overcome the two disadvantages. As compared with the conjugate without the two linkers, the conjugate with the two linkers (E-PS-4) elicited high E protein-specific IgG titers and low beta-glucan-specific IgG titers. E-PS-4 elicited high levels of IFN-gamma, TNF-alpha, IL-2, and IL-10. Moreover, E-PS-4 greatly facilitated the activation of dendritic cells without significant toxicity to the organs. A pharmacokinetic study revealed that the serum duration of E-PS-4 was longer than that of E protein. Accordingly, conjugation of E protein with beta-glucan by the hydrazone and disulfide linkers could promote a potent cellular and humoral immune response to E protein. Thus, our study could facilitate the development of an effective vaccine against ZIKV. |
| WOS关键词 | DRUG-DELIVERY ; ADJUVANT ; VACCINE ; PH ; PRODRUG ; ANTIGEN |
| 资助项目 | National Key Research and Development Project of China[2018YFA0900804] ; National Natural Science Foundation of China[31970875] ; National Natural Science Foundation of China[81703445] ; National Natural Science Foundation of China[81700181] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000538337600014 |
| 出版者 | AMER CHEMICAL SOC |
| 资助机构 | National Key Research and Development Project of China ; National Natural Science Foundation of China |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/41069]  |
| 专题 | 中国科学院过程工程研究所 |
| 通讯作者 | Xu, Junjie; Hu, Tao |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 2.Beijing Inst Biotechnol, Lab Vaccine & Antibody Engn, Beijing 100071, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qi, Jinming,Yin, Ying,Yu, Weili,et al. Conjugation of beta-Glucan with the Hydrazone and Disulfide Linkers Markedly Improves the Immunogenicity of Zika Virus E Protein[J]. MOLECULAR PHARMACEUTICS,2020,17(6):1933-1944. |
| APA | Qi, Jinming,Yin, Ying,Yu, Weili,Shen, Lijuan,Xu, Junjie,&Hu, Tao.(2020).Conjugation of beta-Glucan with the Hydrazone and Disulfide Linkers Markedly Improves the Immunogenicity of Zika Virus E Protein.MOLECULAR PHARMACEUTICS,17(6),1933-1944. |
| MLA | Qi, Jinming,et al."Conjugation of beta-Glucan with the Hydrazone and Disulfide Linkers Markedly Improves the Immunogenicity of Zika Virus E Protein".MOLECULAR PHARMACEUTICS 17.6(2020):1933-1944. |
入库方式： OAI收割
来源：过程工程研究所
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