Enhancement of the immunogenicity of synthetic carbohydrates by conjugation to virosomes: A leishmaniasis vaccine candidate

被引:65
作者
Liu, Xinyu
Siegrist, Sibylle
Amacker, Mario
Zurbriggen, Rinaldo
Pluschke, Gerd
Seeberger, Peter H.
机构
[1] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland
[2] Swiss Trop Inst, CH-4002 Basel, Switzerland
[3] Pevion Biotech Ltd, CH-3018 Bern, Switzerland
关键词
D O I
10.1021/cb600086b
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Novel virosomal formulations of a synthetic oligosaccharicle were prepared and evaluated as vaccine candidates against leishmaniasis. A lipophosphoglycan-related synthetic tetrasaccharide antigen was conjugated to a phospholipid and to the influenza virus coat protein hemagglutinin. These glycan conjugates were embedded into the lipid membrane of reconstituted influenza virus virosomes. The virosomal formulations elicited both IgM and IgG anti-glycan antibodies in mice, indicating an antibody isotype class switch to IgG. The antisera cross-reacted in vitro with the corresponding natural carbohydrate antigens expressed by leishmania cells. These findings support the concept of using virosomes as universal antigen delivery platform for synthetic carbohydrate vaccines.
引用
收藏
页码:161 / 164
页数:4
相关论文
共 32 条
[1]   Oligosaccharide and glycoprotein Microarrays as tools in HIV glycobiology: Glycan-dependent gp120/protein interactions [J].
Adams, EW ;
Ratner, DM ;
Bokesch, HR ;
McMahon, JB ;
O'Keefe, BR ;
Seeberger, PH .
CHEMISTRY & BIOLOGY, 2004, 11 (06) :875-881
[2]   N-pentenyl glycoside methodology in the stereoselective construction of the tetrasaccharyl cap portion of Leishmania lipophosphoglycan [J].
Arasappan, A ;
FraserReid, B .
JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (07) :2401-2406
[3]   Carbohydrate vaccines [J].
Borman, S .
CHEMICAL & ENGINEERING NEWS, 2004, 82 (32) :31-35
[4]  
Danishefsky SJ, 2000, ANGEW CHEM INT EDIT, V39, P836, DOI 10.1002/(SICI)1521-3773(20000303)39:5<836::AID-ANIE836>3.0.CO
[5]  
2-I
[6]   Functional aspects of the Leishmania donovani lipophosphoglycan during macrophage infection [J].
Descoteaux, A ;
Turco, SJ .
MICROBES AND INFECTION, 2002, 4 (09) :975-981
[7]   Toward fully synthetic carbohydrate-based HIV antigen design: On the critical role of bivalency [J].
Dudkin, VY ;
Orlova, M ;
Geng, XD ;
Mandal, M ;
Olson, WC ;
Danishefsky, SJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (31) :9560-9562
[8]   Glycobiology: Toward understanding the function of sugars [J].
Dwek, RA .
CHEMICAL REVIEWS, 1996, 96 (02) :683-720
[9]  
Ernst B., 2000, CARBOHYDRATES CHEM 1, V1
[10]   In vitro cultivation and characterization of axenic amastigotes of Leishmania [J].
Gupta, N ;
Goyal, N ;
Rastogi, AK .
TRENDS IN PARASITOLOGY, 2001, 17 (03) :150-153