Immunogenicity and Diagnostic Potential of Synthetic Antigenic Cell Surface Glycans of Leishmania

被引:33
作者
Anish, Chakkumkal [1 ]
Martin, Christopher E. [1 ,2 ]
Wahlbrink, Annette [1 ]
Bogdan, Christian [3 ]
Ntais, Pantelis [4 ]
Antoniou, Maria [4 ]
Seeberger, Peter H. [1 ,2 ]
机构
[1] Max Planck Inst Colloids & Interfaces, D-14424 Potsdam, Germany
[2] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany
[3] Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Klin Mikrobiol Immunol & Hyg, Mikrobiol Inst, D-91054 Erlangen, Germany
[4] Univ Crete, Fac Med, Lab Clin Bacteriol Parasitol Zoonoses & Geog Med, Iraklion, Greece
关键词
DIRECT AGGLUTINATION-TEST; SAND FLY INTERACTIONS; MONOCLONAL-ANTIBODIES; VISCERAL LEISHMANIASIS; VACCINE CANDIDATE; LIPOPHOSPHOGLYCAN; DONOVANI; AMASTIGOTES; OLIGOSACCHARIDE; PHOSPHOGLYCANS;
D O I
10.1021/cb400602k
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Detection and quantification of pathogen-derived antigenic structures is a key method for the initial diagnosis and follow-up of various infectious diseases. Complex parasitic diseases such as leishmaniasis require highly sensitive and specific tests prior to treatment with potentially toxic drugs. To investigate the diagnostic potential of cell surface glycans found on Leishmania parasites, we identified diagnostically relevant glycan epitopes and used synthetic glycan microarrays to screen sera from infected humans and dogs. On the basis of the screening results, we selected a tetrasaccharide to generate anti-glycan antibodies. The corresponding tetrasaccharide-carrier protein conjugate was immunogenic in mice, and sera obtained from immunized mice specifically detected the Leishmania parasite. These results demonstrate how synthetic glycan arrays, in combination with immunological methods, help to identify promising carbohydrate antigens for pathogen detection.
引用
收藏
页码:2412 / 2422
页数:11
相关论文
共 44 条
[1]
Assis R. R., 2012, PLOS NEGL TROP DIS D, P6
[2]
A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design [J].
Avci, Fikri Y. ;
Li, Xiangming ;
Tsuji, Moriya ;
Kasper, Dennis L. .
NATURE MEDICINE, 2011, 17 (12) :1602-U115
[3]
Early detection of Leishmania promastigotes in dog bone marrow cultures by acridine orange stain [J].
Barreca, GS ;
Matera, G ;
De Majo, M ;
Lamberti, A ;
Liberto, MC ;
Focà, A .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2000, 37 (04) :247-251
[4]
Leishmaniasis in rheumatology, haematology and oncology: epidemiological, immunological and clinical aspects and caveats [J].
Bogdan, Christian .
ANNALS OF THE RHEUMATIC DISEASES, 2012, 71 :60-66
[5]
The immunogenicity of the tumor-associated antigen Lewisy may be suppressed by a bifunctional cross-linker required for coupling to a carrier protein [J].
Buskas, T ;
Li, YH ;
Boons, GJ .
CHEMISTRY-A EUROPEAN JOURNAL, 2004, 10 (14) :3517-3524
[6]
Deficiency in beta 1,3-galactosyltransferase of a Leishmania major lipophosphoglycan mutant adversely influences the Leishmania sand fly interaction [J].
Butcher, BA ;
Turco, SJ ;
Hilty, BA ;
Pimenta, PF ;
Panunzio, M ;
Sacks, DL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (34) :20573-20579
[7]
Visceral leishmaniasis: What are the needs for diagnosis, treatment and control? [J].
Chappuis, Francois ;
Sundar, Shyam ;
Hailu, Asrat ;
Ghalib, Hashim ;
Rijal, Suman ;
Peeling, Rosanna W. ;
Alvar, Jorge ;
Boelaert, Marleen .
NATURE REVIEWS MICROBIOLOGY, 2007, 5 (11) :873-882
[8]
Glycoconjugates in New World species of Leishmania: Polymorphisms in lipophosphoglycan and glycoinositolphospholipids and interaction with hosts [J].
de Assis, Rafael Ramiro ;
Ibraim, Izabela Coimbra ;
Nogueira, Paula Monalisa ;
Soares, Rodrigo Pedro ;
Turco, Salvatore J. .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2012, 1820 (09) :1354-1365
[9]
AN ANTIGENICALLY DISTINCT LIPOPHOSPHOGLYCAN ON AMASTIGOTES OF LEISHMANIA-MAJOR [J].
GLASER, TA ;
MOODY, SF ;
HANDMAN, E ;
BACIC, A ;
SPITHILL, TW .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1991, 45 (02) :337-344
[10]
PRETREATMENT AND POSTTREATMENT ANTIBODY-LEVELS IN VISCERAL LEISHMANIASIS [J].
HAILU, A .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1990, 84 (05) :673-675