β-glucan particles as oral carriers for a dual-antigen hepatitis B vaccine: Liver targeting and immune potentiation following subcutaneous priming.

Chronic hepatitis B virus (HBV) infection is characterized by an inadequate immune response to clearing the virus. Immunomodulatory agents present a promising therapeutic strategy for the treatment of HBV. Glucan particles (GPs), when used as a vaccine adjuvant, have shown the ability to enhance both innate and adaptive immune responses. Thus, we assessed the effectiveness of the GPs-based hepatitis B vaccine in boosting the immune response against HBV. Through biodistribution studies in mice, we confirmed GPs liver accumulation after oral administration. The investigation of GP-hepatocyte interactions revealed that GPs induce elevated production of reactive oxygen species (ROS) in HepG2 cells without affecting cellular glutathione levels. Additionally, GPs promoted the maturation of human dendritic cells (CD80, CD86, MHC-I and MHC-II). Vaccination studies in mice with GPs encapsulating HBsAg, HBcAg, and CL097, a TLR7 agonist, elicited a robust cellular immune response, characterized by enhanced cytotoxic T cell functions, cytokine production, and spleen cell proliferation. Moreover, high levels of serum anti-HBsAg IgG and antigen-specific fecal sIgA were also induced. Notably, the GP-based vaccine also enhanced IFN-γ in the liver. These findings highlight the potential of oral administered GPs for liver targeting and their immunostimulatory properties in the context of hepatitis B vaccination.