Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria.
Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria.
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疟疾流行地区的儿童对疾病具有自然获得的免疫力，这一事实支持了疟疾疫苗的可行性。疾病免疫力的发展的特征是尽管几乎连续感染，但疾病发作的频率和严重程度在几年内下降，这表明免疫力可能通过获得针对多态性靶抗原的特异性保护性抗体库而发展。恶性疟原虫红细胞膜蛋白1（PfEMP 1）是一个潜在的重要的靶抗原家族，因为这些蛋白质被插入到红细胞表面，并显着暴露，因为它们是高度多态性的，并经历克隆抗原变异，免疫逃避的机制，由一个大家族的var基因。在一项对肯尼亚儿童的大型前瞻性研究中，我们使用了抗PfEMP1抗体以特异性变体方式凝集受感染红细胞的事实，以表明在临床疟疾发作期间表达的PfEMP1变体不太可能被相应儿童自身先前存在的抗体应答识别，而不是来自同一社区的同龄儿童。相比之下，异源寄生虫分离株同样可能被识别。已建立的抗PfEMP1抗体对感染寄生虫施加的明显选择性压力支持这样的反应提供针对疾病的变体特异性保护的想法。
The feasibility of a malaria vaccine is supported by the fact that children in endemic areas develop naturally acquired immunity to disease. Development of disease immunity is characterized by a decrease in the frequency and severity of disease episodes over several years despite almost continuous infection, suggesting that immunity may develop through the acquisition of a repertoire of specific, protective antibodies directed against polymorphic target antigens. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of target antigens, because these proteins are inserted into the red cell surface and are prominently exposed and because they are highly polymorphic and undergo clonal antigenic variation, a mechanism of immune evasion maintained by a large family of var genes. In a large prospective study of Kenyan children, we have used the fact that anti-PfEMP1 antibodies agglutinate infected erythrocytes in a variant-specific manner, to show that the PfEMP1 variants expressed during episodes of clinical malaria were less likely to be recognized by the corresponding child’s own preexisting antibody response than by that of children of the same age from the same community. In contrast, a heterologous parasite isolate was just as likely to be recognized. The apparent selective pressure exerted by established anti-PfEMP1 antibodies on infecting parasites supports the idea that such responses provide variant-specific protection against disease.
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DOI：
10.1084/jem.168.4.1307
发表时间：
1988-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Magowan C;Wollish W;Anderson L;Leech J
通讯作者：
Leech J
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ
影响因子：
56.9
作者：
MARSH, K;HOWARD, RJ
通讯作者：
HOWARD, RJ
DOI：
10.1080/00034983.1996.11813067
发表时间：
1996-08-01
影响因子：
--
作者：
Molineaux, L
通讯作者：
Molineaux, L
DOI：
10.4269/ajtmh.1994.51.45
发表时间：
1994-07-01
影响因子：
3.3
作者：
REEDER, JC;ROGERSON, SJ;BROWN, GV
通讯作者：
BROWN, GV