HBV antigen and DNA loss from mouse serum is associated with novel vaccine-induced HBV surface antigen-specific cell-mediated immunity and cytokine production.

Therapeutic vaccination is a promising strategy for controlling chronic hepatitis B virus (HBV). Here, we tested whether several novel vaccination strategies could be used to induce HBV-specific adaptive immune responses and control/eradicate HBV in a mouse model. Robust HBV antigen-specific antibody responses were elicited by several vaccination strategies using a novel particle vaccine (HBSS1), which expresses a fusion of the S (amino acids [aa] 1-223) and preS1 (aa 21-47) antigens, and/or a recombinant adenovirus rAdSS1 vaccine. However, antigen-specific cell-mediated immunity and high levels of production of multiple cytokines were elicited only by heterologous prime-boost immunization; i.e., priming with the HBSS1 vaccine followed by a rAdSS1 boost. Furthermore, the most rapid loss of serum HBsAg, HBeAg and DNA was achieved by the novel vaccination regimen (priming with HBSS1 formulated with adjuvants [alum plus PolyI:C]), which was strongly associated with more potent and functional HBsAg-specific CD4+ and CD8+ T-cell responses and increased production of interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor-α, IL-12, and IFN-γ-induced protein (IP)-10. Thus, our novel heterogeneous prime-boost vaccine regimen shows promise as a therapeutic strategy against HBV.