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Conjugation with an Inulin-Chitosan Adjuvant Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein
Yu, Weili1,2; He, Tao1
2016-11-01
发表期刊MOLECULAR PHARMACEUTICS
ISSN1543-8384
卷号13期号:11页码:3626-3635
摘要

Protein-based vaccines are of potential to deal with the severe situations posed by Mycobacterium tuberculosis (Mtb). Due to inherently poor immunogenicity of Mtb protein antigens, a potent immunostimulatory adjuvant is needed to enhance the cellular and humoral immune response to Mtb protein antigens. Inulin and chitosan (Cs) are polysaccharide adjuvants that can be used to achieve such an objective. The inulin-Cs conjugate (inulin-Cs) acted as a potent adjuvant through a synergistic interaction of inulin and Cs. CFP10 and TB10.4 are two important virulent protein antigens of Mtb. The CFP10-TB10.4 fusion protein (CT) was constructed and used as the protein antigen. In the present study, an adjuvant delivery system (inulin-Cs-CT) was developed by covalent conjugation of CT with inulin-Cs. Conjugation with inulin-Cs significantly increased the hydrodynamic volume of CT and did not alter the structure of CT. High levels of Thl-type cytokines (IFN-gamma, TNF-alpha, and IL-2) and Th2-type cytokine (IL-4) were secreted by provocation of inulin-Cs-CT. Inulin Cs CT elicited high CT-specific antibody titers, mostly in the form of IgG1 and IgG2b. Pharmacokinetics revealed that conjugation with inulin-Cs could prolong the serum exposure of CT to the immune system. Pharmacodynamics suggested that conjugation with inulin-Cs led to an efficient production of CT-specific IgG. Thus, conjugation of inulin-Cs can serve as a potent adjuvant delivery system to improve the immunogenicity of the Mtb protein antigens.

关键词Mycobacterium Tuberculosis Inulin Chitosan Adjuvant Delivery System Subunit Vaccine
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.1021/acs.molpharmaceur.6b00138
收录类别SCI
语种英语
关键词[WOS]IMMUNE-RESPONSES ; EFFICIENT PROTECTION ; VACCINE ; ANTIGEN ; EFFICACY ; CELL ; NANOPARTICLES ; COMPONENTS ; SYSTEM ; MODEL
WOS研究方向Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS类目Medicine, Research & Experimental ; Pharmacology & Pharmacy
项目资助者Beijing Natural Science Foundation(7142104) ; National Natural Science Foundation of China(20906095 ; Science and Technology Service Network Initiative Project of Chinese Academy of Sciences(KFJ-EW-STS-027 ; 81402861) ; KFJ-EW-STS098)
WOS记录号WOS:000387428300003
引用统计
被引频次:6[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/122111/21652
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, 1 Bei Er Tiao St, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100190, Peoples R China
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Yu, Weili,He, Tao. Conjugation with an Inulin-Chitosan Adjuvant Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein[J]. MOLECULAR PHARMACEUTICS,2016,13(11):3626-3635.
APA Yu, Weili,&He, Tao.(2016).Conjugation with an Inulin-Chitosan Adjuvant Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein.MOLECULAR PHARMACEUTICS,13(11),3626-3635.
MLA Yu, Weili,et al."Conjugation with an Inulin-Chitosan Adjuvant Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein".MOLECULAR PHARMACEUTICS 13.11(2016):3626-3635.
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