Ferreira Marcelo U, Zilversmit Martine, Wunderlic Gerhard
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Curr Mol Med. 2007 Sep;7(6):588-602. doi: 10.2174/156652407781695756.
Each year, malaria parasites cause more than 500 million infections and 0.5-3 million deaths worldwide, mostly among children under five living in sub-Saharan Africa. In contrast with several viral and bacterial pathogens, which elicit long-lived immunity after a primary infection, these parasites require several years of continuous exposure to confer partial, usually non-sterilizing immune protection. One of the main obstacles to the acquisition of antimalarial immunity is the high degree of antigenic diversity in potential target antigens, which enables parasites to evade immune responses elicited by past exposure to variant forms of the same antigen. Allelic polymorphism, the existence of genetically stable alternative forms of antigen-coding genes, originates from nucleotide replacement mutations and intragenic recombination. In addition, malaria parasites display antigenic variation, whereby a clonal lineage of parasites expresses successively alternate forms of an antigen without changes in genotype. This review focuses on molecular and evolutionary processes that promote allelic polymorphism and antigenic variation in natural malaria parasite populations and their implications for naturally acquired immunity and vaccine development.
每年，疟原虫在全球导致超过5亿人感染，造成50万至300万人死亡，其中大多数是撒哈拉以南非洲地区的五岁以下儿童。与几种病毒和细菌病原体不同，这些病原体在初次感染后可引发长期免疫，而疟原虫需要持续接触数年才能提供部分（通常是非无菌的）免疫保护。获得抗疟免疫的主要障碍之一是潜在靶抗原的高度抗原多样性，这使得疟原虫能够逃避过去接触同一抗原变体形式所引发的免疫反应。等位基因多态性，即抗原编码基因的遗传稳定替代形式的存在，源于核苷酸替代突变和基因内重组。此外，疟原虫表现出抗原变异，即寄生虫的克隆谱系依次表达抗原的交替形式，而基因型不变。本综述重点关注促进天然疟原虫种群中等位基因多态性和抗原变异的分子和进化过程，以及它们对自然获得性免疫和疫苗开发的影响。
