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Conjugation Reaction with 8-Arm PEG Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein
Sun, Xiaowei1,2; Yu, Weili2; Pang, Quanhai1; Hu, Tao2
2017-06-01
发表期刊BIOCONJUGATE CHEMISTRY
ISSN1043-1802
卷号28期号:6页码:1658-1668
摘要Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for tuberculosis (TB). Effective vaccination is highly desired for immunoprotection against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb-secreted protein antigens, which suffer from poor immunogenicity. Thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. A CFP10-TB10.4 fusion protein (CT) was used as the antigen in the present study. Conjugation of 4-6 CT molecules in one entity with 8-arm polyethylene glycol (PEG) acted as an antigen delivery system. Aluminum-loxoribine mixture (A-L) and poly(I:C) functioned as the adjuvants. As compared with CT, the polymerized CT (CT-PEG) elicited significantly higher CT-specific IgG titers, higher Th1- and Th2-type cytokines and higher percentages of CD4(+) and CD4+ IFN-gamma(+) IL-4(+) cells in BALB/c mice. The presence of A-L and poly(I:C) could both increase the immune response to CT-PEG. Conjugation reaction with 8-arm PEG showed a predominant driving force to improve the immunogenicity of CT. Pharmacokinetic study in SD rats revealed that conjugation reaction with 8-arm PEG prolonged the systemic circulation of CT and exposure to the immune system. CT PEG with A-L showed no apparent toxicity to organs, whereas CT-PEG with poly(I:C) displayed some toxicity to organs. Thus, an effective and safe vaccine against Mtb infection could be rationally designed by conjugation reaction of Mtb-secreted protein antigen with 8-arm PEG and subsequent addition of A-L.
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences
DOI10.1021/acs.bioconjchem.7b00131
收录类别SCI
语种英语
关键词[WOS]MEDIATED IMMUNITY ; DELIVERY-SYSTEM ; CELL-ACTIVATION ; VACCINE ; ADJUVANT ; ANTIGEN ; NANOPARTICLES ; INFECTION ; PROSPECTS ; EFFICACY
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
WOS类目Biochemical Research Methods ; Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary ; Chemistry, Organic
项目资助者National Natural Science Foundation of China(81402861 ; Beijing Natural Science Foundation(7142104) ; Science and Technology Service Network Initiative Project of Chinese Academy of Sciences(KFJ-EW-STS-027 ; 20906095) ; KFJ-EW-STS098)
WOS记录号WOS:000404090500008
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被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/22700
专题生化工程国家重点实验室
作者单位1.Shanxi Agr Univ, Coll Anim Sci, Taigu 030801, Shanxi Province, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
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Sun, Xiaowei,Yu, Weili,Pang, Quanhai,et al. Conjugation Reaction with 8-Arm PEG Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein[J]. BIOCONJUGATE CHEMISTRY,2017,28(6):1658-1668.
APA Sun, Xiaowei,Yu, Weili,Pang, Quanhai,&Hu, Tao.(2017).Conjugation Reaction with 8-Arm PEG Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein.BIOCONJUGATE CHEMISTRY,28(6),1658-1668.
MLA Sun, Xiaowei,et al."Conjugation Reaction with 8-Arm PEG Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein".BIOCONJUGATE CHEMISTRY 28.6(2017):1658-1668.
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