Kusi Kwadwo A, Manu Emmanuel A, Manful Gwira Theresa, Kyei-Baafour Eric, Dickson Emmanuel K, Amponsah Jones A, Remarque Edmond J, Faber Bart W, Kocken Clemens H M, Dodoo Daniel, Gyan Ben A, Awandare Gordon A, Atuguba Frank, Oduro Abraham R, Koram Kwadwo A
Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
PLoS One. 2017 Sep 25;12(9):e0185303. doi: 10.1371/journal.pone.0185303. eCollection 2017.
Plasmodium falciparum induced antibodies are key components of anti-malarial immunity in malaria endemic areas, but their antigen targets can be polymorphic. Induction of a high proportion of strain-specific antibodies will limit the recognition of a broad diversity of parasite strains by these responses. There are indications that circulating parasite diversity varies with malaria transmission intensity, and this may affect the specificity of elicited anti-malarial antibodies. This study therefore assessed the effect of varying malaria transmission patterns on the specificity of elicited antibody responses and to identify possible antibody correlates of naturally acquired immunity to malaria in children in an area of Ghana with seasonal malaria transmission.
This retrospective study utilized plasma samples collected longitudinally at six time points from children aged one to five years. Multiplex assays were used to measure antibody levels against four P. falciparum AMA 1 variants (from the 3D7, FVO, HB3 and CAMP parasite strains) and the 3D7 variant of the EBA 175 region II antigen and the levels compared between symptomatic and asymptomatic children. The relative proportions of cross-reactive and strain-specific antibodies against the four AMA 1 variants per sampling time point were assessed by Bland-Altman plots. The levels of antibodies against allelic AMA1 variants, measured by singleplex and multiplex luminex assays, were also compared.
The data show that increased transmission intensity is associated with higher levels of cross-reactive antibody responses, most likely a result of a greater proportion of multiple parasite clone infections during the high transmission period. Anti-AMA1 antibodies were however associated with a history of infection rather than protection in this age group.
The data contribute to understanding the underlying mechanism of the acquisition of strain-transcending antibody immunity following repeated exposure to diverse parasite strains.
恶性疟原虫诱导产生的抗体是疟疾流行地区抗疟免疫的关键组成部分,但其抗原靶点可能具有多态性。诱导产生高比例的菌株特异性抗体将限制这些反应对多种寄生虫菌株的广泛识别。有迹象表明,循环中的寄生虫多样性随疟疾传播强度而变化,这可能会影响所引发的抗疟抗体的特异性。因此,本研究评估了不同疟疾传播模式对所引发抗体反应特异性的影响,并确定了加纳一个季节性疟疾传播地区儿童自然获得性疟疾免疫的可能抗体相关因素。
这项回顾性研究利用了从1至5岁儿童中纵向收集的六个时间点的血浆样本。采用多重检测法测量针对四种恶性疟原虫AMA 1变体(来自3D7、FVO、HB3和CAMP寄生虫菌株)以及EBA 175区域II抗原的3D7变体的抗体水平,并比较有症状和无症状儿童之间的水平。通过Bland-Altman图评估每个采样时间点针对四种AMA 1变体的交叉反应性抗体和菌株特异性抗体的相对比例。还比较了通过单重和多重Luminex检测法测量的针对等位基因AMA1变体的抗体水平。
数据表明,传播强度的增加与更高水平的交叉反应性抗体反应相关,这很可能是高传播期多重寄生虫克隆感染比例更高的结果。然而,在这个年龄组中,抗AMA1抗体与感染史相关,而非与保护作用相关。
这些数据有助于理解反复接触多种寄生虫菌株后获得菌株超越性抗体免疫的潜在机制。