Tanner M, Alonso P L
Swiss Tropical Institute, Department of Public Health and Epidemiology, Basel.
Schweiz Med Wochenschr. 1996 Jul 9;126(27-28):1210-5.
Malaria, especially that caused by Plasmodium falciparum, is the most important parasitic disease of man. The complexity of the life cycle, the transmission dynamics in different endemic settings, and the spread of resistance to various drugs by the parasite and to insecticides by the vector render control strategies very difficult. An effective vaccine against malaria would represent a major strengthening of control. Research efforts to identify and select antigens for vaccine development have been substantial, particularly in the past 20 years. Various molecules from the pre-erythrocytic, asexual blood and sexual stages have been described and tested in experimental systems, and some may become interesting vaccine candidates. A crucial step was taken with the development of SPf66, a synthetic polypeptide based on pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. The concept of the SPf66 vaccine is not the prevention of clinical malaria but reduction of morbidity, and it is thus suitable for endemic areas, particularly Africa. The clinical phase III trials so far undertaken in Latin America and in Africa have clearly documented the safety, immunogenicity and partial efficacy of SPf66 against clinical malaria. The efficacy estimates of all trials are below those we generally demand from vaccines and when we aim to induce sterile immunity. Therefore, a large number of issues at the field and laboratory levels, such as ways of optimizing efficacy (doses, timing, age of vaccination), and understanding the mechanisms of action and effectiveness, need to be investigated before one can consider the public health use of SPf66 as a component of an integrated malaria control programme. The substantial tasks ahead involve (1) improving the vaccine which we have and (2) devising and testing new vaccines which may prove more efficacious. Malaria vaccines are now a reality, and the achievements of SPf66 to date, the ongoing research efforts with other vaccine candidates, and the potential of DNA vaccines make it possible to predict that widespread use of an efficacious vaccine no longer represents an unrealistic target.
疟疾，尤其是由恶性疟原虫引起的疟疾，是人类最重要的寄生虫病。疟原虫复杂的生命周期、不同流行地区的传播动态，以及寄生虫对各种药物和媒介对杀虫剂耐药性的传播，使得控制策略非常困难。一种有效的疟疾疫苗将极大地加强疟疾控制。特别是在过去20年里，为确定和选择用于疫苗开发的抗原所做的研究工作一直很多。来自疟原虫前红细胞期、无性血液期和有性期的各种分子已在实验系统中得到描述和测试，其中一些可能成为有前景的疫苗候选物。基于恶性疟原虫前红细胞期和无性血液期蛋白的合成多肽SPf66的研发迈出了关键一步。SPf66疫苗的理念不是预防临床疟疾，而是降低发病率，因此适用于流行地区，尤其是非洲。迄今为止在拉丁美洲和非洲进行的III期临床试验已清楚地证明了SPf66针对临床疟疾的安全性、免疫原性和部分疗效。所有试验的疗效估计均低于我们通常对疫苗的要求以及我们旨在诱导无菌免疫时的要求。因此，在考虑将SPf66作为综合疟疾控制计划的一部分用于公共卫生之前，需要在现场和实验室层面研究大量问题，例如优化疗效的方法（剂量、接种时间、接种年龄），以及了解其作用机制和有效性。未来的重要任务包括：（1）改进我们现有的疫苗；（2）设计和测试可能更有效的新疫苗。疟疾疫苗现在已成为现实，SPf66迄今为止所取得的成果、对其他疫苗候选物正在进行的研究工作以及DNA疫苗的潜力，使人们有可能预测，广泛使用一种有效的疫苗不再是一个不切实际的目标。
