title: Aptamer against mannose-capped lipoarabinomannan inhibits virulent Mycobacterium tuberculosis infection in mice and rhesus monkeys.
abstract: The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose-capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb. We used systematic evolution of ligands by exponential enrichment (SELEX) to generate an aptamer (ZXL1) that specifically bound to ManLAM from the virulent M. tb strain H37Rv. Aptamer ZXL1 had the highest binding affinity, with an equilibrium dissociation constant (Kd) of 436.3 ± 37.84 nmol/l, and competed with the mannose receptor for binding to ManLAM and M. tb H37Rv. ZXL1 significantly inhibited the ManLAM-induced immunosuppression of CD11c(+) dendritic cells (DCs) and enhanced the M. tb antigen-presenting activity of DCs for naive CD4(+) Th1 cell activation. More importantly, we demonstrated that injection of aptamer ZXL1 significantly reduced the progression of M. tb H37Rv infections and bacterial loads in lungs of mice and rhesus monkeys. These results suggest that the aptamer ZXL1 is a new potential antimycobacterial agent and tuberculosis vaccine immune adjuvant.
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Xianru
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Laboratory Medicine, Wuhan Medical Treatment Center, Wuhan, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Fengling
authors.initials: F
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008358:Mannose / Q000235:genetics / Q000276:immunology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014376:Tuberculosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: D052157:Aptamers, Nucleotide; D000939:Epitopes; D008070:Lipopolysaccharides; D032581:Tuberculosis Vaccines; C050016:lipoarabinomannan; D008358:Mannose