title: Synthesis and antigenicity of BBGL-2 glycolipids of Borrelia burgdorferi, the causative agent of Lyme disease.
abstract: Borrelia burgdorferi is the etiological agent for Lyme disease (LD), the most common vector borne disease in the United States. There is no human vaccine against LD currently available. Our approach to a vaccine is based on its surface-exposed glycolipids. One group of these glycolipids termed BBGL-2 consists of 1,2-di-O-acyl-3-O-(α-d-galactopyranosyl)-sn-glycerol congeners having palmitic, oleic, stearic, linoleic, and myristic acids. In order to delineate the immunodominant region(s) of the BBGL-2 components, we embarked on a synthetic project to provide available structurally defined, homogeneous analogs of BBGL-2 that might help identify the best vaccine candidate. The antigenicity of the synthetic glycolipids was examined by dot-blot analysis using mice sera obtained by immunization with killed B. burgdorferi cells, with native BBGL-2 in complete Freund's adjuvant, as well as sera obtained from patients with Lyme disease. We found that the presence of two acyl groups in the glycerol moiety was essential for antigenicity. At least one of these groups must be an oleoyl moiety. Neither the anomeric configuration of the galactose nor the configuration of the glycerol at C-2 was a decisive factor. Based on these findings we designed an 'unnatural' BBGL-2 analog having the structure 3-O-(β-d-galactopyranosyl)-1,2-di-O-oleoyl-dl-glycerol which is easier and less expensive to synthesize than the other BBGL-2 congeners prepared in this study. This substance proved to be antigenic and is considered a candidate vaccine for Lyme disease.
authors: Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892-2423, United States. pozsgayv@mail.nih.gov
authors: Vince
authors: V
authors: Pozsgay
authors: Joanna
authors: J
authors: Kubler-Kielb
authors: Bruce
authors: B
authors: Coxon
authors: Adriana
authors: A
authors: Marques
authors: John B
authors: JB
authors: Robbins
authors: Rachel
authors: R
authors: Schneerson
references: J Biol Chem. 2003 Sep 5;278(36):33645-53
references: 12810705
references: Epidemiol Infect. 2007 Jan;135(1):1-8
references: 16893489
references: N Engl J Med. 1998 Jul 23;339(4):209-15
references: 9673298
references: J Biol Chem. 2009 May 15;284(20):13326-13334
references: 19307181
references: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1535-40
references: 20080535
references: Clin Infect Dis. 2011 Feb;52 Suppl 3:s271-5
references: 21217175
references: Carbohydr Res. 2003 May 1;338(10):1073-81
references: 12706973
references: Carbohydr Res. 1998 Jan;306(1-2):81-91
references: 9691441
references: Med Microbiol Immunol. 1991;180(5):229-37
references: 1722277
references: Biochimie. 2001 Jul;83(7):683-92
references: 11522398
references: Clin Infect Dis. 2011 Feb;52 Suppl 3:s247-52
references: 21217171
references: J Org Chem. 2010 Aug 6;75(15):4891-8
references: 20387787
references: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7913-8
references: 12799465
references: Nature. 1997 Dec 11;390(6660):580-6
references: 9403685
references: FEMS Microbiol Immunol. 1991 Feb;3(1):33-8
references: 1711876
references: MMWR Surveill Summ. 2008 Oct 3;57(10):1-9
references: 18830214
references: Nat Immunol. 2006 Sep;7(9):978-86
references: 16921381
references: Clin Immunol. 2009 Jul;132(1):93-102
references: 19342303
references: Infect Immun. 1991 Dec;59(12):4450-8
references: 1937803
references: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1351-6
references: 15665086
references: Carbohydr Res. 2007 Feb 26;342(3-4):621-6
references: 17182019
references: Chem Commun (Camb). 2007 Jun 21;(23):2336-8
references: 17844738
references: J Infect Dis. 1993 Mar;167(3):665-74
references: 8440937
references: Arthritis Rheum. 2009 Apr;60(4):1179-86
references: 19333928
references: Org Biomol Chem. 2006 Jun 21;4(12):2358-60
references: 16763679
references: Science. 1998 Jul 31;281(5377):703-6
references: 9685265
references: Infect Immun. 1987 Sep;55(9):2311-3
references: 3623705
references: Science. 1982 Jun 18;216(4552):1317-9
references: 7043737