Nardin E H, Nussenzweig R S
Department of Medical and Molecular Parasitology, New York University School of Medicine, NY 10010.
Annu Rev Immunol. 1993;11:687-727. doi: 10.1146/annurev.iy.11.040193.003351.
Malaria remains a leading cause of human morbidity and mortality due to the inability of insecticides and chemotherapy/chemoprophylaxis to eliminate the vectors or disease caused by this protozoan parasite. In an effort to develop new methods of control, vaccines targeted to the various stages of the complex life cycle of Plasmodium have been developed. This review describes recent advances in the elucidation of cell-mediated immune mechanisms directed against sporozoites and liver stages of malaria parasites, their role in protection, and their relation to vaccine development. Recent data on the molecular basis of sporozoite-liver cell interaction are presented, and these may provide new approaches for chemoprophylaxis and immunoprophylaxis. We describe the role of the circumsporozoite protein, the major sporozoite surface antigen, in sporozoite movement and as a target of humoral immunity. The recognition of the circumsporozoite protein by human T cells is reviewed with emphasis on cytotoxic T cells and immune resistance against the exo-erythrocytic stage of the parasite. Earlier concepts regarding the polymorphisms of the circumsporozoite protein, the immunological relevance of this polymorphism, and predictions regarding vaccine development are reevaluated on the basis of recent data from different malaria endemic areas. Non-CS sporozoite antigens and liver stage antigens are discussed as potential targets for immune intervention. Recent experimental approaches such as multiple antigen peptides, recombinant live vectors, and new more potent adjuvants are considered for the development of more effective malaria vaccine formulations.
由于杀虫剂以及化学疗法/化学预防法无法消灭疟原虫寄生虫所引起的病媒或疾病，疟疾仍然是导致人类发病和死亡的主要原因。为了开发新的控制方法，针对疟原虫复杂生命周期各个阶段的疫苗已经研制出来。这篇综述描述了在阐明针对疟原虫子孢子和肝期的细胞介导免疫机制、它们在保护中的作用以及它们与疫苗开发的关系方面的最新进展。文中展示了关于子孢子-肝细胞相互作用分子基础的最新数据，这些数据可能为化学预防和免疫预防提供新方法。我们描述了环子孢子蛋白（主要的子孢子表面抗原）在子孢子移动中的作用以及作为体液免疫靶点的作用。综述了人类T细胞对环子孢子蛋白的识别，重点是细胞毒性T细胞以及对寄生虫红细胞外期的免疫抗性。基于来自不同疟疾流行地区的最新数据，重新评估了关于环子孢子蛋白多态性的早期概念、这种多态性的免疫学相关性以及关于疫苗开发的预测。讨论了非环子孢子蛋白子孢子抗原和肝期抗原作为免疫干预潜在靶点的情况。为了开发更有效的疟疾疫苗制剂，考虑了多种抗原肽、重组活载体和新型更有效的佐剂等最新实验方法。
