Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study
文献类型:期刊论文
作者 | Qi, Jinming1,2; He, Yunxia1,2; Shen, Lijuan1; Yu, Weili1; Hu, Tao1 |
刊名 | BIOCONJUGATE CHEMISTRY |
出版日期 | 2021-02-17 |
卷号 | 32期号:2页码:328-338 |
ISSN号 | 1043-1802 |
DOI | 10.1021/acs.bioconjchem.0c00700 |
英文摘要 | Zika virus (ZIKV) leads to congenital microcephaly and anomalies and severe neurological diseases such as Guillain-Barre syndrome. Safe and effective vaccines are necessitated to deal with these severe health threats. As an ideal antigen, the domain III of the envelope protein (EDIII) of ZIKV can evoke potent neutralizing antibodies without any antibody-dependent enhancement (ADE) effect. However, EDIII necessitates to be formulated with an antigen delivery system or adjuvants to improve its immunogenicity. Hemoglobin (Hb) regulates inflammation, cytokine levels, and activate macrophage. Mannan is a polysaccharide of the fungal cell wall with an immunomodulatory activity. In this study, EDIII was conjugated with Hb and mannan, using the disulfide bond as the linker. Hb and mannan both functioned as the adjuvants. Conjugation of Hb and mannan acted as the delivery system for EDIII. The structure of EDIII was essentially maintained upon conjugation of Hb and mannan. The intracellular release of EDIII from the conjugate (HM-EDIII-2) was achieved by reduction of the glutathione-sensitive disulfide bond. As compared with EDIII, HM-EDIII-2 elicited high EDIII-specific IgG titers and high levels of Thl-type cytokines (IFN-gamma and IL-2) and Th2-type cytokines (IL-5 and IL-10), along with no apparent toxicity to the organs. Moreover, the pharmacokinetic study revealed a prolonged serum exposure of HM-EDIII-2 to the immune cells. Thus, HM-EDIII-2 could boost a strong humoral and cellular immune response to EDIII. Our study was expected to provide the feasibility necessary to develop a robust and potentially safe ZIKV vaccine. |
资助项目 | National Natural Science Foundation of China[31970875] ; Beijing Natural Science Foundation[M21013] ; National Key Research and Development Project of China[2018YFA0900804] |
WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
语种 | 英语 |
出版者 | AMER CHEMICAL SOC |
WOS记录号 | WOS:000621366800012 |
资助机构 | National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National Key Research and Development Project of China |
源URL | [http://ir.ipe.ac.cn/handle/122111/47923] |
专题 | 中国科学院过程工程研究所 |
通讯作者 | Hu, Tao |
作者单位 | 1.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100190, Peoples R China |
推荐引用方式 GB/T 7714 | Qi, Jinming,He, Yunxia,Shen, Lijuan,et al. Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study[J]. BIOCONJUGATE CHEMISTRY,2021,32(2):328-338. |
APA | Qi, Jinming,He, Yunxia,Shen, Lijuan,Yu, Weili,&Hu, Tao.(2021).Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study.BIOCONJUGATE CHEMISTRY,32(2),328-338. |
MLA | Qi, Jinming,et al."Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study".BIOCONJUGATE CHEMISTRY 32.2(2021):328-338. |
入库方式: OAI收割
来源:过程工程研究所
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