Protective efficacy and hepatitis B virus clearance in mice enhanced by cell‐mediated immunity with novel prime‐boost regimens

Abstract

In this study, anti-hepatitis B virus (HBV) immunity was evaluated in mice using several regimens of the HBV recombinant protein vaccine HBSS1 that expressed in CHO cells containing S (1-223 aa) and preS1 (21-47 aa) and recombinant adenovirus rAdSS1 vaccine. Further, the protective efficacy of these vaccine regimens was studied in a mouse model. High titres of antigen-specific antibodies and neutralizing activity were elicited in mice after vaccination. However, robust multi-antigen (preS1 and S)-specific cell-mediated immunity (CMI) was only detected in mice primed with HBSS1 and boosted with rAdSS1. Moreover, functional T-cell responses with high levels of cytokines and antigen-specific cytotoxic T-cell responses (CD107a CD8 ) were also detected in the mice. Rapid clearance of hepatitis B surface antigen and HBV DNA in blood and significantly decreased hepatitis B envelope antigen levels were observed in mice immunized with the heterogeneous prime-boost vaccine after hepatitis B virus challenge by hydrodynamic injection (HI) of pCS-HBV1.3. The clearance of HBV correlated well with antigen-specific CMI (Th1 and CTL responses) and cytokine profiles (IFN-γ, TNF-α, IL-2) elicited by vaccination. Taken together, our results might contribute to the development of new human HBV vaccines and a better understanding of the mechanisms underlying immune protection and clearance of hepatitis B virus infection.

Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B

“…In order to improve immunogenicity and efficacy of therapeutic vaccine candidates for chronic HBV infection, others have used a combination of approaches, such as adjuvants, addition of checkpoint inhibitors, and prime/boost regimens (Kosinska et al., 2017, Schinazi et al., 2018). Recent studies showed that an optimized, heterologous prime/boost strategy produced strong T and B responses to HBV in various preclinical models of CHB (Backes et al., 2016, Chuai et al., 2017, Liu et al., 2014). A combination of an HBsAg/HBcAg protein prime with TLR9 agonists followed by a boost with non-replicating modified vaccinia Ankara viruses, optimized for higher level expression of the same antigens, was able to overcome the high-level tolerance observed in HBV-transgenic mice (Backes et al., 2016).…”

Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B

“…In order to improve immunogenicity and efficacy of therapeutic vaccine candidates for chronic HBV infection, others have used a combination of approaches, such as adjuvants, addition of checkpoint inhibitors, and prime/boost regimens (7,9). Recent studies showed that an optimized, heterologous prime/boost strategy produced strong T and B responses to HBV in various preclinical models of CHB (32)(33)(34). A combination of an HBsAg/HBcAg protein prime with TLR9 agonists followed by a boost with non-replicating modified vaccinia Ankara viruses, optimized for higher level expression of the same antigens was able to overcome the high-level tolerance observed in HBV-transgenic mice (34).…”