title: Beta-glycoglycosphingolipid-induced augmentation of the anti-HBV immune response is associated with altered CD8 and NKT lymphocyte distribution: a novel adjuvant for HBV vaccination.
abstract: BACKGROUND
  Non-responsiveness towards the currently used hepatitis B virus (HBV) vaccine is a major problem in attempts to protect against HBV infection. Several methods have been tested to overcome the lack of an effective immune response towards HBV antigens. Adjuvants that augment the immunologic reaction are essential components of the vaccines. Beta-glycosphingolipids exert a natural killer T cell (NKT)-mediated immunomodulatory effect in various disorders.
  
  
  OBJECTIVE
  The aim of the present study was to test the ability of these compounds to augment the immune response towards HBV antigens, making them potential adjuvants for HBV vaccines. Six groups of mice were injected with different formulations of an HBV vaccine, along with various doses of beta-glucosylceramide (beta-GC), beta-lactosylceramide (beta-LC), or a combination of both (IGL) in different doses. The effect of beta-glycosphingolipids on the immune response towards HBV was tested by fluorescence-activated cell sorting analysis of hepatic and splenic NKT and CD8 lymphocytes, and serum cytokine levels.
  
  
  RESULTS
  Beta-sphingolipid treatment altered the hepatic NKT and CD8 lymphocyte distribution. beta-LC, beta-GC, and the combination of both augmented anti-HBV immunity, increasing both the anti-HBs titers and the percentage of mice exhibiting high titers. This effect was associated with altered hepatic NKT and CD8+ lymphocyte distribution.
  
  
  CONCLUSIONS
  In summary, beta-glycosphingolipids increased the anti-HBV immune response in association with an altered NKT and CD8 lymphocyte distribution, making beta-glycosphingolipids potential potent adjuvants for overcoming non-responsiveness to HBV vaccination and augmenting the anti-viral immune response.
authors.affiliation: Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Kiryat Hadassah, Jerusalem, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Mizrahi
authors.forename: Gadi
authors.initials: G
authors.lastname: Lalazar
authors.forename: Ami
authors.initials: A
authors.lastname: Ben Ya'acov
authors.forename: Dan M
authors.initials: DM
authors.lastname: Livovsky
authors.forename: Yuval
authors.initials: Y
authors.lastname: Horowitz
authors.forename: Lidya
authors.initials: L
authors.lastname: Zolotarov
authors.forename: Ruth
authors.initials: R
authors.lastname: Adler
authors.forename: Daniel
authors.initials: D
authors.lastname: Shouval
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005963:Glucosylceramides / Q000494:pharmacology*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007790:Lactosylceramides / Q000494:pharmacology*; D008099:Liver / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005963:Glucosylceramides; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007790:Lactosylceramides