Specific immune response to HBsAg is enhanced by β-glucan oligosaccharide containing an α-(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 β-(1→6)-branched β-(1→3) glucohexaose is the basic unit of lentinan and several other fungal β-glucans with immunostimulatory activity. β-glucans stimulate innate immune response mainly through interaction with myeloid cells (macrophages) and dendritic cells.In this study, the ability of synthetic β-(1→6)-branched β-(1→3) glucohexaose analogue (β-glu6) to enhance the immune response to HBsAg has been evaluated. Administration of synthetic β-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 β-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. β-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-γ-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 β-glu6 as a vaccine adjuvant. The IgG1/IgG2a ratio within the anti-HBsAg antibodies was higher in the mice immunised with HBsAg plus β-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.