Calcineurin B subunit triggers innate immunity and acts as a novel Engerix-B® HBV vaccine adjuvant

Abstract

We showed previously that calcineurin B subunit (CnB) protein activates innate immune cells including macrophages, monocytes and dendritic cells and acts as an adjuvant of a model antigen (ovalbumin) and a recombinant pneumolysin antigen, but the detailed mechanism is not clear and whether it can serve as an adjuvant of a commercial HBV vaccine is unknown. Here, we report that CnB promotes inflammatory cytokines production, splenocytes proliferation and NK lytic activity, and that CnB-induced inflammatory cytokines (IFN-γ, IL-6, TNF-α) production is dependent on integrin αM. Animal experiments demonstrate that CnB markedly increases the total anti-HBs antibodies in a dose and time dependent manner. Furthermore, CnB increases both anti-HBs IgM and anti-HBs IgG titers and changes the balance of IgG2a and IgG1. Combined use of CnB and CpG induces more cytokines production in splenocytes, as well as more anti-HBs antibodies production in vivo. These results reveal a probable mechanism of CnB-induced inflammatory cytokines production and further demonstrate that CnB is a novel and effective adjuvant of Engerix-B® HBV vaccine.