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首页> 外文期刊>Vaccine >Pf332-C231-reactive antibodies affect growth and development of intra-erythrocytic Plasmodium falciparum parasites.
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Pf332-C231-reactive antibodies affect growth and development of intra-erythrocytic Plasmodium falciparum parasites.

机译：Pf332-C231反应性抗体影响红细胞内恶性疟原虫的寄生虫的生长和发育。

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The Plasmodium falciparum antigen 332 (Pf332), is a megadalton parasite protein expressed at the surface of infected red cells during later stages of the parasite's developmental cycle. Antibodies to different parts of this antigen have been shown to inhibit parasite growth and adherence to host cells with or without ancillary cells. However, the mechanisms involved in these inhibitions remain largely unknown. We further analysed the activities of specific antibodies with regard to their specific mechanisms of action. For these analyses, affinity purified human antibodies against epitopes in the C-terminal fragment of Pf332 (Pf332-C231) were employed. All purified antibodies recognized Pf332-C231 both by immunofluorescence and ELISA. IgG was the main antibody isotype detected, although all sera investigated had varying proportions of IgG and IgM content. All the antibodies showed a capacity to inhibit parasite growth in P. falciparum cultures to different extents, mainly by acting on the more mature parasite stages. Morphological analysis revealed the antibody effects to be characterized by the presence of a high proportion of abnormal schizonts (15-30%) and pyknotic parasites. There was also an apparent antibody effect on the red cell integrity, as many developing parasites (up to 10% of trophozoites and schizonts) were extracellular. In some cases, the infected red cells appeared to be disintegrating/fading, staining paler than surrounding infected and uninfected cells. Antigen reversal of inhibition confirmed that these inhibitions were antigen specific. Furthermore, the growth of parasites after 22-42 h exposure to antibodies was investigated. Following the removal of antibody pressure, a decreased growth rate of these parasites was seen compared to that of control parasites. The present study confirms the potential of Pf332 as a target antigen for parasite neutralizing antibodies, and further indicates that epitopes within the C231 region of Pf332 should constitute important tools in the dissection of the role of Pf332 in the biology of the malaria parasite, as well as in the design of a malaria vaccine.
机译：恶性疟原虫抗原332（Pf332）是一种在寄生虫发育周期后期在受感染的红细胞表面表达的megadalton寄生虫蛋白。已经显示出针对该抗原不同部分的抗体可以抑制寄生虫的生长以及对带有或不带有辅助细胞的宿主细胞的粘附。然而，这些抑制作用所涉及的机制仍是未知之数。我们就其特定的作用机理进一步分析了特定抗体的活性。对于这些分析，使用针对Pf332（Pf332-C231）C-末端片段中的表位的亲和纯化的人抗体。所有纯化的抗体均通过免疫荧光和ELISA识别Pf332-C231。 IgG是检测到的主要抗体同种型，尽管研究的所有血清具有不同比例的IgG和IgM含量。所有抗体均显示出抑制P中寄生虫生长的能力。恶性疟原虫的培养程度不同，主要是通过作用于更成熟的寄生虫阶段。形态学分析显示，该抗体作用的特征在于存在高比例的异常裂殖体（15％至30％）和强直性寄生虫。由于许多发育中的寄生虫（多达10％的滋养体和裂殖体）在细胞外，对红细胞的完整性也有明显的抗体作用。在某些情况下，被感染的红细胞似乎会崩解/褪色，比周围被感染和未被感染的细胞的染色更浅。抑制的抗原逆转证实这些抑制是抗原特异性的。此外，研究了暴露于抗体22-42小时后寄生虫的生长。去除抗体压力后，与对照寄生虫相比，这些寄生虫的生长速率下降。本研究证实了Pf332作为寄生虫中和抗体的靶抗原的潜力，并进一步表明Pf332的C231区域内的表位也应构成重要的工具，以剖析Pf332在疟原虫生物学中的作用就像设计疟疾疫苗一样。

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