Heterologous prime-boost immunization with vesiculovirus-based vectors expressing HBV core antigen induces CD8+ T cell responses in naïve and persistently infected mice and protects from challenge

In this study, we evaluated the immunogenicity and efficacy of two attenuated vesiculovirus-based platforms expressing HBV Core antigen, the highly attenuated vesicular stomatitis virus (VSV) N4CT1 and a unique vaccine platform [virus-like vesicles (VLV)] that is based on a Semliki Forest virus replicon expressing the VSV glycoprotein. We found that heterologous prime-boost immunization with VLV and N4CT1 induced specific CD8+ T cell responses to Core in naïve mice. When immunized mice were later challenged with AAV-HBV, functional Core-specific CD8+ T cells were present in the liver, and mice were protected from establishment of persistent infection. In contrast, when mice with pre-established persistent HBV replication received prime-boost immunization, functional Core-specific CD8+ T cells were found in the spleen but not in the liver. These results highlight the importance of investigating the therapeutic value of different HBV antigens alone and in combination using preclinical animal models, and understanding the correlation between anti-HBV efficacy in these models with human infection.
Source: Antiviral Therapy - Category: Virology Source Type: research