Vanderberg Jerome P
Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, USA.
Vaccine. 2009 Jan 1;27(1):2-9. doi: 10.1016/j.vaccine.2008.10.028. Epub 2008 Oct 28.
Advances towards protective vaccines against malaria were made feasible by the development of a rodent model of mammalian malaria that allowed production of all stages of the malaria parasite for study. Investigations with sporozoites (the stage transmitted by mosquitoes in their saliva) demonstrated that immunization with radiation-attenuated sporozoites could produce a solid, sterile immunity, first shown in studies with mice and later with human volunteers. Protective immune mechanisms involve anti-sporozoite antibodies that immobilize sporozoites injected into the skin by mosquitoes, followed by CD4+ and CD8+ T-cells acting against liver stage parasites produced by sporozoites that have escaped antibody-based immunity and invaded hepatocytes. Two alternative approaches now being used in human trials are immunization with intact, attenuated sporozoites vs. immunization with "sub-unit" vaccines based on immunogenic components of sporozoites or liver stage parasites. In addition to immunization against these pre-erythrocytic stages, encouraging progress is being made on immunization against blood stage parasites and on immunization for production of transmission-blocking antibodies. There is reason to be optimistic that one or more of the approaches will work on a large scale, and that a multi-stage vaccine may be able to combine several of these approaches in a sequential immunological assault against the malaria parasite as it progresses through its stages.
哺乳动物疟疾啮齿动物模型的开发使得研制抗疟疾保护性疫苗成为可能，该模型能够培育出疟原虫的各个阶段用于研究。对子孢子（蚊子唾液中传播的阶段）的研究表明，用辐射减毒子孢子免疫可产生可靠的无菌免疫力，这一现象首先在小鼠研究中得到证实，随后在人类志愿者研究中也得到了验证。保护性免疫机制包括抗子孢子抗体，该抗体可使蚊子注入皮肤的子孢子失去活性，随后CD4+和CD8+ T细胞作用于逃脱基于抗体免疫并侵入肝细胞的子孢子所产生的肝期寄生虫。目前正在人体试验中使用的两种替代方法是用完整的减毒子孢子免疫与用基于子孢子或肝期寄生虫免疫原性成分的“亚单位”疫苗免疫。除了针对这些红细胞前期阶段进行免疫外，在针对血期寄生虫的免疫以及产生传播阻断抗体的免疫方面也取得了令人鼓舞的进展。有理由乐观地认为，这些方法中的一种或多种将大规模发挥作用，并且多阶段疫苗或许能够在疟原虫经历其各个阶段时，通过一系列免疫攻击将其中几种方法结合起来对抗疟原虫。
