title: Specific immune response to HBsAg is enhanced by beta-glucan oligosaccharide containing an alpha-(1-->3)-linked bond and biased towards M2/Th2.
abstract: Vaccination with Hepatitis B surface antigen (HBsAg) is being used to prevent HBV infection. The fact that 10% of vaccinees fail to develop protective antibodies has fostered a large body of research for more effective vaccination strategies. Search for new adjuvant, able to selectively trigger protective antibody production, is one of the most promising approaches. The oligosaccharide beta-(1-->6)-branched beta-(1-->3) glucohexaose is the basic unit of lentinan and several other fungal beta-glucans with immunostimulatory activity. beta-glucans stimulate innate immune response mainly through interaction with myeloid cells (macrophages) and dendritic cells. In this study, the ability of synthetic beta-(1-->6)-branched beta-(1-->3) glucohexaose analogue (beta-glu6) to enhance the immune response to HBsAg has been evaluated. Administration of synthetic beta-glu6 i.p. in BALB/c mice greatly enhanced the mobilisation and maturation of macrophages and dendritic cells to co-administered HBsAg, as compared to the antigen alone. The adjuvant effect of beta-glu6 was evident in the increase of T and B cell activation in response to HBsAg, as judged by the percentage of CD69-positive CD4(+) and CD19(+) lymphocytes in the spleen. beta-glu6 could significantly enhance the number of IL-4-producing cells in response to HBsAg, while it had no effect on the number of IFN-gamma-producing lymphocytes, suggesting a Th2 bias of the immune response. The correlate of protection for HBV vaccination, i.e. the titer of HBsAg-specific antibodies, was greatly enhanced by the use of beta-glu6 as a vaccine adjuvant. The IgG1/IgG2a ratio within the anti-HBsAg antibodies was higher in the mice immunised with HBsAg plus beta-glu6 than receiving HBsAg alone or mice administered HBsAg with Freund's adjuvant, indicating a shift towards a Th2-biased anti-inflammatory protective antibody response.
authors.affiliation: Key laboratory of Medical Molecular Virology, the Shanghai Medical College of Fudan University, Shanghai, PR China.
authors.forename: Sheng-Fu
authors.initials: SF
authors.lastname: Dong
authors.forename: Jie-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Gu
authors.forename: Diana
authors.initials: D
authors.lastname: Boraschi
authors.forename: Di
authors.initials: D
authors.lastname: Qu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000494:pharmacology*; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D047071:beta-Glucans / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D047071:beta-Glucans; D015847:Interleukin-4; D007371:Interferon-gamma