Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV-specific humoral and CTL immune responses in vivo

• Ub-HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-γ and IL-2.
• Ub-HBcAg-CTP induced higher percentages of IFN-γ+CD8+ cells and specific CTL responses.
• The specific CTL response was associated with the activation of JAK/STAT signaling pathway.
• The fusion protein may offer a potential therapeutic strategy for CHB.

Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker of protein degradation, may promote the generation of peptides appropriate for major histocompatibility complex class I presentation. In the present study, the specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were evaluated and the underlying mechanisms were investigated. Results showed that Ub-HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-γ and IL-2. This fusion protein also induced higher percentages of IFN-γ+CD8+ cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub-HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV-specific CTL activities in BALB/c mice.