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Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate
Huang, Qingrui1,2; Yu, Weili1,2; Hu, Tao1
2016-04-01
发表期刊BIOCONJUGATE CHEMISTRY
ISSN1043-1802
卷号27期号:4页码:1165-1174
摘要Protein-based vaccine is promising to improve or replace Mycobacterium bovis BCG vaccine for its specificity, safety, and easy production. However, protein-based vaccine calls for potent adjuvants and improved delivery systems to protect against Mycobacterium tuberculosis. Poly(I:C) is one of the most potent pathogen-associated molecular patterns that signals primarily via TLR3. Arabinogalactan (AG) is a biocompatible polysaccharide that can increase splenocyte proliferation and stimulate macrophages. The AG-poly(I:C) conjugate (AG-P) showed an adjuvant potency through a synergistic interaction of AG and poly(I:C). Ag85B and HspX are two important virulent protein antigens of Mycobacterium tuberculosis and Ag85B-HspX fusion protein (AH) was prepared. An antigen-adjuvant delivery system (AH-AG-P) was developed by conjugation of AH with AG-P to ensure that both AH and AG-P reach the APCs simultaneously. AH-AG-P elicited high AH-specific IgG titers and stimulated lymphocyte proliferation. AH-AG-P provoked the secretion of Th1-type cytokines (TNF-alpha, IFN-gamma, and IL-2) and Th2-type cytokines (IL-4 and IL-10). Pharmacokinetics revealed that conjugation with AG-P could prolong the serum exposure of AH to the immune system. Pharmacodynamics suggested that conjugation with AG-P led to a rapid and intense production of AH-specific IgG. Accordingly, conjugation with AG-P could promote a robust cellular and humoral immune response to AH. Thus, conjugation of AH with a potent adjuvant AG-P is an effective strategy to develop an efficacious protein-based vaccine against Mycobacterium tuberculosis.
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences
DOI10.1021/acs.bioconjchem.6b00116
收录类别SCI
语种英语
关键词[WOS]RESISTANT TUBERCULOSIS ; MULTIDRUG-RESISTANT ; VACCINE DEVELOPMENT ; IMMUNOGENICITY ; POLYSACCHARIDE ; EFFICACY ; IMPROVES ; IMMUNE ; MODEL ; TIME
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-STS-098)
WOS记录号WOS:000374812600034
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/21012
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100190, Peoples R China
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Huang, Qingrui,Yu, Weili,Hu, Tao. Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate[J]. BIOCONJUGATE CHEMISTRY,2016,27(4):1165-1174.
APA Huang, Qingrui,Yu, Weili,&Hu, Tao.(2016).Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate.BIOCONJUGATE CHEMISTRY,27(4),1165-1174.
MLA Huang, Qingrui,et al."Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate".BIOCONJUGATE CHEMISTRY 27.4(2016):1165-1174.
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