Nielsen Morten A, Staalsoe Trine, Kurtzhals Jørgen A L, Goka Bamenla Q, Dodoo Daniel, Alifrangis Michael, Theander Thor G, Akanmori Bartholomew D, Hviid Lars
Center for Medical Parasitology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
J Immunol. 2002 Apr 1;168(7):3444-50. doi: 10.4049/jimmunol.168.7.3444.
In areas of endemic parasite transmission, protective immunity to Plasmodium falciparum malaria is acquired over several years with numerous disease episodes. Acquisition of Abs to parasite-encoded variant surface Ags (VSA) on the infected erythrocyte membrane is important in the development of immunity, as disease-causing parasites appear to be those not controlled by preexisting VSA-specific Abs. In this work we report that VSA expressed by parasites from young Ghanaian children with P. falciparum malaria were commonly and strongly recognized by plasma Abs from healthy children in the same area, whereas recognition of VSA expressed by parasites from older children was weaker and less frequent. Independent of this, parasites isolated from children with severe malaria (cerebral malaria and severe anemia) were better recognized by VSA-specific plasma Abs than parasites obtained from children with nonsevere disease. This was not due to a higher infection multiplicity in younger patients or in patients with severe disease. Our data suggest that acquisition of VSA-specific Ab responses gradually restricts the VSA repertoire that is compatible with parasite survival in the semi-immune host. This appears to limit the risk of severe disease by discriminating against the expression of VSA likely to cause life-threatening complications, such as cerebral malaria and severe anemia. Such VSA seem to be preferred by parasites infecting a nonimmune host, suggesting that VSA expression and switching are not random, and that the VSA expression pattern is modulated by immunity. This opens the possibility of developing morbidity-reducing vaccines targeting a limited subset of common and particularly virulent VSA.
在寄生虫传播的流行地区，对恶性疟原虫疟疾的保护性免疫是在数年中通过多次发病而获得的。获得针对感染红细胞膜上寄生虫编码的可变表面抗原（VSA）的抗体在免疫发展中很重要，因为致病寄生虫似乎是那些不受预先存在的VSA特异性抗体控制的寄生虫。在这项工作中，我们报告称，来自患有恶性疟原虫疟疾的加纳幼儿的寄生虫所表达的VSA，被同一地区健康儿童的血浆抗体普遍且强烈地识别，而来自年龄较大儿童的寄生虫所表达的VSA的识别则较弱且频率较低。与此无关的是，与从非重症疾病儿童获得的寄生虫相比，从患有重症疟疾（脑型疟疾和严重贫血）的儿童分离出的寄生虫被VSA特异性血浆抗体识别得更好。这并非由于年轻患者或重症患者的感染复数更高。我们的数据表明，获得VSA特异性抗体反应逐渐限制了与半免疫宿主中寄生虫存活相容的VSA库。这似乎通过区分可能导致危及生命的并发症（如脑型疟疾和严重贫血）的VSA的表达来限制重症疾病的风险。这种VSA似乎是感染非免疫宿主的寄生虫所偏好的，这表明VSA的表达和转换不是随机的，并且VSA的表达模式受免疫调节。这为开发针对有限子集的常见且特别有毒力的VSA的降低发病率的疫苗开辟了可能性。
