Nahrendorf Wiebke, Scholzen Anja, Sauerwein Robert W, Langhorne Jean
Mill Hill Laboratory, The Francis Crick Institute, London, United Kingdom; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Vaccine. 2015 Dec 22;33(52):7513-7. doi: 10.1016/j.vaccine.2015.09.098. Epub 2015 Oct 19.
A vaccine against malaria is urgently needed for control and eventual eradication. Different approaches are pursued to induce either sterile immunity directed against pre-erythrocytic parasites or to mimic naturally acquired immunity by controlling blood-stage parasite densities and disease severity. Pre-erythrocytic and blood-stage malaria vaccines are often seen as opposing tactics, but it is likely that they have to be combined into a multi-stage malaria vaccine to be optimally safe and effective. Since many antigenic targets are shared between liver- and blood-stage parasites, malaria vaccines have the potential to elicit cross-stage protection with immune mechanisms against both stages complementing and enhancing each other. Here we discuss evidence from pre-erythrocytic and blood-stage subunit and whole parasite vaccination approaches that show that protection against malaria is not necessarily stage-specific. Parasites arresting at late liver-stages especially, can induce powerful blood-stage immunity, and similarly exposure to blood-stage parasites can afford pre-erythrocytic immunity. The incorporation of a blood-stage component into a multi-stage malaria vaccine would hence not only combat breakthrough infections in the blood should the pre-erythrocytic component fail to induce sterile protection, but would also actively enhance the pre-erythrocytic potency of this vaccine. We therefore advocate that future studies should concentrate on the identification of cross-stage protective malaria antigens, which can empower multi-stage malaria vaccine development.
迫切需要一种疟疾疫苗来控制并最终根除疟疾。人们采取了不同的方法来诱导针对红细胞前期寄生虫的无菌免疫，或通过控制血期寄生虫密度和疾病严重程度来模拟自然获得的免疫。红细胞前期和血期疟疾疫苗通常被视为相互对立的策略，但很可能必须将它们组合成一种多阶段疟疾疫苗，才能达到最佳的安全性和有效性。由于肝期和血期寄生虫之间存在许多共同的抗原靶点，疟疾疫苗有可能通过免疫机制引发跨阶段保护，两个阶段的免疫机制相互补充和增强。在此，我们讨论来自红细胞前期和血期亚单位及全寄生虫疫苗接种方法的证据，这些证据表明对疟疾的保护不一定具有阶段特异性。特别是在肝期后期停滞的寄生虫，可诱导强大的血期免疫，同样，接触血期寄生虫也可提供红细胞前期免疫。因此，在多阶段疟疾疫苗中加入血期成分，不仅可以在红细胞前期成分未能诱导无菌保护时对抗血液中的突破性感染，还可以积极增强该疫苗的红细胞前期效力。因此，我们主张未来的研究应集中于鉴定跨阶段保护性疟疾抗原，这可以推动多阶段疟疾疫苗的研发。
