Interleukin-12 (IL-12) plays an important role in antigen-specific adaptive immunity against Plasmodium sporozoites， and this requirement allows for a new approach to developing an effective malaria vaccine. In this study， we examined whether IL-12 could enhance protective efficacy of a baculovirus-based malaria vaccine. For this aim， a baculoviral vector expressing murine IL-12 (mIL-12) under the control of CMV promoter (BES-mIL-12-Spider) and a baculoviral vector expressing Plasmodium falciparum circumsporozoite protein (PfCSP) with post-transcriptional regulatory element of woodchuck hepatitis virus (BDES-sPfCSP2-WPRE-Spider) were generated. BES-mIL-12-Spider produced bioactive IL-12 which activates sp... More
Interleukin-12 (IL-12) plays an important role in antigen-specific adaptive immunity against Plasmodium sporozoites， and this requirement allows for a new approach to developing an effective malaria vaccine. In this study， we examined whether IL-12 could enhance protective efficacy of a baculovirus-based malaria vaccine. For this aim， a baculoviral vector expressing murine IL-12 (mIL-12) under the control of CMV promoter (BES-mIL-12-Spider) and a baculoviral vector expressing Plasmodium falciparum circumsporozoite protein (PfCSP) with post-transcriptional regulatory element of woodchuck hepatitis virus (BDES-sPfCSP2-WPRE-Spider) were generated. BES-mIL-12-Spider produced bioactive IL-12 which activates splenocytes， resulting in induction of IFN-γ. When co-immunized with BES-mIL-12-Spider and BDES-sPfCSP2-WPRE-Spider， the mouse number for high IgG2a/IgG1 ratios and the geometric mean in this group were both increased as compared with those of the other groups， indicating a shift towards a Th1-type response following immunization with BES-mIL-12-Spider. Finally， immunization with BDES-sPfCSP2-WPRE-Spider plus BES-mIL-12-Spider had a higher protective efficacy (73%) than immunization with BDES-sPfCSP2-WPRE-Spider alone (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. These results suggest that co-administration of IL-12 expressing baculoviral vector， instead of IL-12 cDNA， with viral-vectored vaccines provides a new feasible vaccine platform to enhance Th1-type cellular immune responses against Plasmodium parasites.
