Cohen S
Proc R Soc Lond B Biol Sci. 1979 Jan 15;203(1153):323-45. doi: 10.1098/rspb.1979.0001.
Malaria remains prevalent throughout tropical and subtropical regions and almost a third of the World's population is exposed to the risk of infection. There is currently a serious resurgence of the disease in Asia and Central America. The failure of global eradication measures based upon the use of insecticides and chemotherapy has resulted from difficulties of practical implementation compounded by the spread of insecticide and drug resistance. Repeated natural infection does not produce detectable resistance to the exo-erythrocytic cycle of malaria in man. Irradiated sporzoite vaccines do, however, induce stage specific immunity in murine malaria and in a proportion of human subjects. Vaccinated individuals remain susceptible to blood stage infection which causes clinical malaria. In addition the vaccine is unstable and must be administered by intravenous inoculation. Since neither sporogonic nor exo-erythrocytic parasite development is cyclical in human malarias, there is little prospect for vaccine production through cultivation of these stages. The inhabitants of hyperendaemic areas become increasingly resistant to malaria during childhood and adolescence, through the slow development of specific, acquired immunity to asexual blood stage parasites. Immunity is mediated by antibody, which blocks merozoite invasion of red cells, as well as by cell mediated mechanisms and non-specific cytotoxic agents. Vaccination with merozoites induces long lasting immunity of broad serological specificity active against the blood-stage of the parasite. Merozoite vaccines can be preserved by freeze drying and harvested from continuous cultures of blood stage parasites. The major problem in development of a human merozoite vaccine concerns the requirement for Freund's complete adjuvant which is not acceptable for man. The effective immunity induced by vaccination contrasts with the slow development of incomplete resistance which follows repeated natural infection. The latter is associated with the generation of immune suppressor cells, lymphoid cell mitogens and soluble antigens, and in some species by the occurrence of antigenic variation--all of which may favour parasite survival. It is probable that vaccination with non-viable antigen of appropriate composition, induces immune effector processes without activating mechanisms which allow parasites to escape the consequences of immunity. Many effective vaccines such as those against measles, poliomyelitis, tetanus and rabies are commercially available but barely used in the developing world. The affected nations cannot afford their purchase, nor do the means exist for their distribution. It follows that if a safe and effective malaria vaccine were to be developed, its bulk manufacture and administration would require massive international support and cooperation.
疟疾在热带和亚热带地区仍然普遍存在，世界上近三分之一的人口面临感染风险。目前，亚洲和中美洲该疾病正在严重复发。基于杀虫剂和化疗的全球根除措施失败，是由于实际实施困难，再加上杀虫剂和耐药性的传播。反复自然感染不会使人对疟疾的红细胞外期产生可检测到的抗性。然而，经辐射的子孢子疫苗确实能在鼠疟和一部分人类受试者中诱导阶段特异性免疫。接种疫苗的个体仍然易患导致临床疟疾的血液阶段感染。此外，该疫苗不稳定，必须通过静脉注射给药。由于在人类疟疾中，孢子生殖和红细胞外期寄生虫发育都不是周期性的，通过培养这些阶段来生产疫苗的前景渺茫。在高度流行地区，居民在童年和青少年时期对疟疾的抵抗力会逐渐增强，这是通过对无性血液阶段寄生虫的特异性获得性免疫的缓慢发展实现的。免疫由抗体介导，抗体可阻止裂殖子侵入红细胞，也由细胞介导机制和非特异性细胞毒性剂介导。用裂殖子接种疫苗可诱导具有广泛血清学特异性的持久免疫，对寄生虫的血液阶段有活性。裂殖子疫苗可以通过冷冻干燥保存，并从血液阶段寄生虫的连续培养物中收获。开发人类裂殖子疫苗的主要问题在于需要弗氏完全佐剂，而这对人类是不可接受的。接种疫苗诱导的有效免疫与反复自然感染后缓慢发展的不完全抗性形成对比。后者与免疫抑制细胞、淋巴细胞有丝分裂原和可溶性抗原的产生有关，在某些物种中还与抗原变异有关——所有这些都可能有利于寄生虫存活。用适当组成的无活力抗原接种疫苗，可能会诱导免疫效应过程，而不会激活使寄生虫逃避免疫后果的机制。许多有效的疫苗，如麻疹、脊髓灰质炎、破伤风和狂犬病疫苗，都有商业供应，但在发展中国家几乎未被使用。受灾国家买不起这些疫苗，也没有分发它们的手段。因此，如果要开发一种安全有效的疟疾疫苗，其大规模生产和接种将需要大量的国际支持与合作。
