Iyori M, Blagborough A M, Sala K A, Nishiura H, Takagi K, Yoshida S
Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan.
Department of Life Sciences, Imperial College London, London, UK.
Parasite Immunol. 2017 Dec;39(12). doi: 10.1111/pim.12498.
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.
白细胞介素-12（IL-12）在针对疟原虫子孢子的抗原特异性适应性免疫中发挥重要作用，这一需求为开发有效的疟疾疫苗提供了新方法。在本研究中，我们检测了IL-12是否能增强基于杆状病毒的疟疾疫苗的保护效力。为此，构建了一种在巨细胞病毒（CMV）启动子控制下表达小鼠IL-12（mIL-12）的杆状病毒载体（BES-mIL-12-Spider）和一种表达恶性疟原虫环子孢子蛋白（PfCSP）并带有旱獭肝炎病毒转录后调控元件的杆状病毒载体（BDES-sPfCSP2-WPRE-Spider）。BES-mIL-12-Spider产生具有生物活性的IL-12，可激活脾细胞，导致干扰素-γ的诱导。当与BES-mIL-12-Spider和BDES-sPfCSP2-WPRE-Spider共同免疫时，该组中高IgG2a/IgG1比值的小鼠数量和几何平均值均高于其他组，表明用BES-mIL-12-Spider免疫后向Th1型反应转变。最后，用BDES-sPfCSP2-WPRE-Spider加BES-mIL-12-Spider免疫对表达PfCSP的转基因伯氏疟原虫子孢子攻击的保护效力（73%）高于单独用BDES-sPfCSP2-WPRE-Spider免疫（30%）。这些结果表明，将表达IL-12的杆状病毒载体而非IL-12 cDNA与病毒载体疫苗共同给药，为增强针对疟原虫的Th1型细胞免疫反应提供了一个新的可行疫苗平台。
