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Isolation and expression of UB05, a Plasmodium falciparum antigen recognised by antibodies from semi-immune adults in a high transmission endemic area of the Cameroonian rainforest

机译:分离和表达UB05,一种恶性疟原虫抗原,由喀麦隆雨林高传播流行区的半免疫成体抗体识别

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摘要

Background: Antibodies in adults living in malaria endemic areas that target specific parasite antigens are implicated in protective immunity to infection and disease. This study aimed to identify, isolate and characterise targets of protective immunity in malaria. A Plasmodium falciparum antigen termed UB05 (Genbank Accession Number DQ235690: PlasmoDB PF10_ 0372) that had been isolated by immunoscreening with semi-immune sera was studied. Methods: Polymerase chain reaction, sequencing and bioinformatics were used to analyse the UB05 gene. A specific mouse anti-UB05 antibody was used in parasite reinvasion growth/inhibition assays and in immunoflourescence to localise the antigen. In a cross-sectional study, enzyme linked immunosorbent assay was used to study immunoglobulin G (IgG) responses to the antigen. Results: The gene revealed significant homologies with gene sequences from Plasmodia and other apicomplexan parasites and had two alleles in the wild P. falciparum isolates. The antigen is expressed by schizonts and segmented merozoites. Mouse antibodies against it marginally inhibit in vitro invasion of erythrocytes by P. falciparum. The IgG responses to UB05 were found to be significantly lower (p<0.05) in the sera of children (2–5 years) compared with adults (>18 years), with or without parasitaemia. However, parasitaemia correlated inversely (r=0.7– 0.75) with serum anti-UB05 IgG concentrations. Furthermore, anti-UB05 IgG concentrations were lower in the sera of febrile patients (body temperature >37.5°C) than their non-febrile counterparts regardless of parasitaemia status. Conclusions: These results are compatible with a role for UB05 in the development of immunity and as a marker of protective immunity to malaria. Clin Chem Lab Med 2009;47:1147–58.
机译:背景:生活在疟疾流行地区的成年人中针对特定寄生虫抗原的抗体与针对感染和疾病的保护性免疫有关。这项研究旨在鉴定,分离和表征疟疾中保护性免疫的靶标。研究了一种恶性疟原虫抗原,称为UB05(Genbank登录号DQ235690:PlasmoDB PF10_0372),该抗原已通过半免疫血清进行免疫筛选而分离。方法:采用聚合酶链反应,测序和生物信息学方法分析UB05基因。特异的小鼠抗UB05抗体用于寄生虫侵袭生长/抑制测定和免疫荧光法中以定位抗原。在横断面研究中,酶联免疫吸附测定法用于研究免疫球蛋白G(IgG)对抗原的反应。结果:该基因与疟原虫和其他apicomplexan寄生虫的基因序列显示出显着的同源性,并且在野生恶性疟原虫分离物中有两个等位基因。抗原由裂殖体和分段裂殖子表达。针对它的小鼠抗体略微抑制恶性疟原虫在体外对红细胞的侵袭。与成人(> 18岁)(有或没有寄生虫病)相比,儿童(2-5岁)的血清中对UB05的IgG应答明显降低(p <0.05)。但是,寄生虫血症与血清抗UB05 IgG浓度呈负相关(r = 0.7-0.75)。此外,不论寄生虫血症状态如何,发热患者(体温> 37.5°C)血清中的抗UB05 IgG浓度均低于非发热患者的血清。结论:这些结果与UB05在免疫发展中的作用以及作为对疟疾的保护性免疫的标志物是相容的。临床化学实验室杂志2009; 47:1147–58。

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