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Pf 155,一种恶性疟原虫疟疾血液阶段疫苗的候选物。

Pf 155, a candidate for a blood stage vaccine in Plasmodium falciparum malaria.

作者信息

Berzins K, Perlmann H, Udomsangpetch R, Wåhlin B, Wahlgren M, Troye-Blomberg M, Carlsson J, Björkman A, Perlmann P

出版信息

Dev Biol Stand. 1985;62:99-106.

PMID:3914427
Abstract

Pf 155 is a Mr 155,000 P. falciparum antigen, which is deposited in the erythrocyte membrane at merozoite invasion. The antigen is detected by a modified immunofluorescence assay giving staining of the surface of ring stage infected erythrocytes. Cell lines producing human monoclonal antibodies to Pf 155 were established and two different antibodies of IgM and IgG class, respectively, were characterized further. Both antibodies gave a strong surface immunofluorescence and in immunoblotting they react strongly with Pf 155, but also with some lower molecular weight material, including polypeptides of Mr 135,000 and 120,000. Both antibodies were efficient inhibitors of P. falciparum reinvasion in vitro. Pf 155 as well as the Mr 135,000 and 120,000 polypeptides were shown to bind with high affinity to human erythrocyte glycophorin. An octapeptide (GluGluAsnValGluHisAspAla) corresponding to a repeated sequence in Pf 155 was synthesized. Rabbit antibodies to the octapeptide gave a distinct surface immunofluorescence and reacted with Pf 155 and the Mr 135,000 and 120,000 polypeptides in immunoblotting. Human antibodies reacting with the octapeptide were isolated by affinity chromatography from the serum of a P. falciparum immune individual. These antibodies showed a strong reaction with Pf 155 as determined by immunoblotting and surface immunofluorescence. Pf 155 reactive antibodies affinity purified on monolayers of P. falciparum infected erythrocytes are very efficient inhibitors of parasite reinvasion. Such antibody preparations depleted of octapeptide reactive antibodies showed a markedly decreased reinvasion inhibitory capacity, while a high inhibitory activity was recovered in the octapeptide reactive antibodies. Pf 155 fulfills several criteria thought to be proper for antigens involved in anti-malarial protective immunity.

摘要

Pf 155是一种分子量为155,000的恶性疟原虫抗原,在裂殖子侵入时沉积于红细胞膜。该抗原通过改良免疫荧光测定法检测,可使环状体期感染红细胞的表面染色。建立了产生针对Pf 155的人单克隆抗体的细胞系,并对分别属于IgM和IgG类别的两种不同抗体进行了进一步表征。两种抗体均产生强烈的表面免疫荧光,在免疫印迹中它们与Pf 155强烈反应,但也与一些较低分子量的物质反应,包括分子量为135,000和120,000的多肽。两种抗体都是体外恶性疟原虫再侵入的有效抑制剂。Pf 155以及分子量为135,000和120,000的多肽显示与人类红细胞血型糖蛋白具有高亲和力结合。合成了与Pf 155中重复序列相对应的八肽(GluGluAsnValGluHisAspAla)。针对该八肽的兔抗体产生明显的表面免疫荧光,并在免疫印迹中与Pf 155以及分子量为135,000和120,000的多肽反应。通过亲和层析从恶性疟原虫免疫个体的血清中分离出与该八肽反应的人抗体。通过免疫印迹和表面免疫荧光测定,这些抗体与Pf 155显示出强烈反应。在恶性疟原虫感染红细胞单层上亲和纯化的Pf 155反应性抗体是寄生虫再侵入的非常有效的抑制剂。这种去除了八肽反应性抗体的抗体制剂显示出再侵入抑制能力明显降低,而八肽反应性抗体中恢复了高抑制活性。Pf 155符合被认为适用于抗疟疾保护性免疫所涉及抗原的几个标准。

相似文献

1
Pf 155, a candidate for a blood stage vaccine in Plasmodium falciparum malaria.Pf 155,一种恶性疟原虫疟疾血液阶段疫苗的候选物。
Dev Biol Stand. 1985;62:99-106.
2
Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion.针对恶性疟原虫抗原Pf 155的重复氨基酸序列的兔抗体和人抗体,可与天然蛋白发生反应并抑制裂殖子入侵。
Proc Natl Acad Sci U S A. 1986 Feb;83(4):1065-9. doi: 10.1073/pnas.83.4.1065.
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Reactivity of the human monoclonal antibody 33G2 with repeated sequences of three distinct Plasmodium falciparum antigens.人单克隆抗体33G2与三种不同恶性疟原虫抗原重复序列的反应性。
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Plasmodium falciparum: analysis of the cytoadherence inhibition of the human monoclonal antibody 33G2 and of antibodies reactive with antigen Pf332.恶性疟原虫:人源单克隆抗体33G2及与抗原Pf332反应的抗体的细胞黏附抑制分析
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Human monoclonal antibodies to Pf 155, a major antigen of malaria parasite Plasmodium falciparum.针对恶性疟原虫主要抗原Pf 155的人源单克隆抗体。
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Recent progress in the development of malaria vaccines: memorandum from a WHO meeting.疟疾疫苗研发的最新进展:世界卫生组织会议纪要
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Plasmodium falciparum: an epitope within a highly conserved region of the 47-kDa amino-terminal domain of the serine repeat antigen is a target of parasite-inhibitory antibodies.恶性疟原虫:丝氨酸重复抗原47 kDa氨基末端结构域高度保守区域内的一个表位是寄生虫抑制性抗体的作用靶点。
Exp Parasitol. 1997 Feb;85(2):121-34. doi: 10.1006/expr.1996.4118.

引用本文的文献

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Regulation of the immune response in Plasmodium falciparum malaria: IV. T cell dependent production of immunoglobulin and anti-P. falciparum antibodies in vitro.恶性疟原虫疟疾免疫反应的调节:IV. 体外T细胞依赖性免疫球蛋白和抗恶性疟原虫抗体的产生
Clin Exp Immunol. 1987 May;68(2):288-97.