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Conjugation of beta-Glucan with the Hydrazone and Disulfide Linkers Markedly Improves the Immunogenicity of Zika Virus E Protein
Qi, Jinming2; Yin, Ying1; Yu, Weili2; Shen, Lijuan2; Xu, Junjie1; Hu, Tao2
2020-06-01
Source PublicationMOLECULAR PHARMACEUTICS
ISSN1543-8384
Volume17Issue:6Pages:1933-1944
AbstractThe 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.
KeywordZika virus beta-glucan E protein adjuvant hydrazine disulfide
DOI10.1021/acs.molpharmaceut.0c00010
Language英语
WOS KeywordDRUG-DELIVERY ; ADJUVANT ; VACCINE ; PH ; PRODRUG ; ANTIGEN
Funding ProjectNational 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 Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
Funding OrganizationNational Key Research and Development Project of China ; National Natural Science Foundation of China
WOS IDWOS:000538337600014
PublisherAMER CHEMICAL SOC
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/41070
Collection中国科学院过程工程研究所
Corresponding AuthorXu, Junjie; Hu, Tao
Affiliation1.Beijing Inst Biotechnol, Lab Vaccine & Antibody Engn, Beijing 100071, Peoples R China
2.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China
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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.
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