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A malaria serological map indicating the intersection between parasite antigenic diversity and host antibody repertoires

机译:疟疾血清学图谱,表明寄生虫抗原多样性与宿主抗体库之间的交集

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摘要

A malaria vaccine targeting Plasmodium falciparum remains a strategic goal for malaria control. If a polyvalent vaccine is to be developed, its subunits would probably be chosen based on immunogenicity (concentration of elicited antibodies) and associations of selected antigens with protection. We propose an additional possible selection criterion for the inclusion of subunit antigens; that is, coordination between elicited antibodies. For the quantitative estimation of this coordination, we developed a malaria serological map (MSM). Construction of the MSM was based on three categories of variables: (i) malaria antigens, (ii) total IgG and IgG subclasses, (iii) different sources of plasma. To validate the MSM, in this study, we used four malaria antigens (AMA1, MSP2-3D7, MSP2-FC27 and Pf332-C231) and re-grouped the plasma samples into five pairs of subsets based on age, gender, residence, HbAS and malaria morbidity in 9 years. The plasma total IgG and IgG subclasses to the test antigens were measured, and the whole material was used for the MSM construction. Most of the variables in the MSM were previously tested and their associations with malaria morbidity are known. The coordination of response to each antigens pair in the MSM was quantified as the correlation rate (CR=overall number of significant correlations/total number of correlations × 100 %). Unexpectedly, the results showed that low CRs were mostly associated with variables linked with malaria protection and the antigen eliciting the least CRs was the one associated with protection. The MSM is, thus, of potential value for vaccine design and understanding of malaria natural immunity.
机译:针对恶性疟原虫的疟疾疫苗仍然是控制疟疾的战略目标。如果要开发多价疫苗,则可能会根据免疫原性(引发抗体的浓度)以及所选抗原与保护的关联来选择其亚基。我们提出了包含亚基抗原的其他可能的选择标准。即,引起的抗体之间的协调。为了定量评估这种协调性,我们开发了疟疾血清学图谱(MSM)。 MSM的构建基于以下三类变量:(i)疟疾抗原,(ii)总IgG和IgG亚类,(iii)不同血浆来源。为了验证MSM,在这项研究中,我们使用了四种疟疾抗原(AMA1,MSP2-3D7,MSP2-FC27和Pf332-C231),并根据年龄,性别,居住,HbAS将血浆样品重新分组为五对子集和9年内的疟疾发病率。测量血浆总IgG和属于测试抗原的IgG亚类,并将整个材料用于MSM构建。 MSM中的大多数变量均已过测试,并且它们与疟疾发病率的关联是已知的。 MSM中对每个抗原对的响应的协调被量化为相关率(CR =显着相关的总数/相关总数×100%)。出乎意料的是,结果表明低CR大多与与疟疾保护相关的变量有关,而引起CR最少的抗原就是与保护有关的抗原。因此,MSM对于疫苗设计和了解疟疾自然免疫具有潜在价值。

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