title: Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate.
abstract: 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-α, IFN-γ, 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.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.|University of Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Huang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.|University of Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Yu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000737:chemistry; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry; D005685:Galactans / Q000737:chemistry*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011066:Poly C / Q000737:chemistry*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005685:Galactans; C118127:HspX protein, Mycobacterium tuberculosis; D011066:Poly C; C005653:arabinogalactan