Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity.
Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity.
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DOI：
10.1016/j.vaccine.2015.10.058
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发表时间：
2016-01-02
期刊：
影响因子：
5.5
通讯作者：
MVVC Infant Immunology Study Group
中科院分区：
文献类型：
--
作者：
Kangoye DT;Mensah VA;Murungi LM;Nkumama I;Nebie I;Marsh K;Cisse B;Bejon P;Osier FH;Sirima SB;MVVC Infant Immunology Study Group
研究了抗体动态及其在婴儿对热性疟疾低易感性中的作用。没有发现抗体滴度与临床保护相关的证据。高传播区和低传播区抗体滴度持续较低的证据。其他抗体、其他抗体介导的机制或其他保护因素可能正在起作用。与年龄较大的儿童相比，年幼的婴儿对热性疟疾的易感性降低，但其机制仍不清楚。关于被动获得抗体的作用，存在相互矛盾的数据。在这里，我们在两种不同疟疾传播强度的环境中检查了裂殖子表面抗原的抗体滴度，以保护出生后两年内的儿童，并将这些滴度与先前建立的保护阈值进行比较。在布基纳法索邦福拉和塞内加尔凯尔索切招募了两组年龄为 4 至 6 周的儿童，并进行了两年的随访。通过对主动和被动病例检测访视时收集的血涂片进行光学显微镜检查来检测疟疾感染。在 1-6、9、12、15 和 18 个月龄时通过酶联免疫吸附测定测量恶性疟原虫重组裂殖子蛋白（AMA1-3D7、MSP1-19、MSP2-Dd2 和 MSP3-3D7）的抗体滴度，并与在肯尼亚儿童中建立的保护阈值进行比较。在整个研究期间，抗体滴度低于保护阈值，我们没有发现与预防热性疟疾有任何关联。在单变量分析中，AMA1 和 MSP1-19 抗体似乎是暴露标记（因此与风险增加相关），并且根据暴露进行调整降低了这种关联的强度和显着性。我们测量的抗体水平不太可能对小婴儿的热性疟疾具有明显的保护作用。识别保护性抗体反应的进一步工作可能包括功能测定和更广泛的抗原。
Antibody dynamics and role in young the infants’ low susceptibility to febrile malaria were investigated. No evidence for association of antibody titres with clinical protection was found. Evidence for consistently low antibody titres in high and low transmission areas. Other antibodies, other antibody-mediated mechanisms or other protecting factors may be operating. Young infants have reduced susceptibility to febrile malaria compared with older children, but the mechanism for this remains unclear. There are conflicting data on the role of passively acquired antibodies. Here, we examine antibody titres to merozoite surface antigens in the protection of children in their first two years of life in two settings with differing malaria transmission intensity and compare these titres to previously established protective thresholds. Two cohorts of children aged four to six weeks were recruited in Banfora, Burkina and Keur Soce, Senegal and followed up for two years. Malaria infections were detected by light microscopic examination of blood smears collected at active and passive case detection visits. The titres of antibodies to the Plasmodium falciparum recombinant merozoite proteins (AMA1-3D7, MSP1-19, MSP2-Dd2, and MSP3-3D7) were measured by enzyme-linked immunosorbent assay at 1–6, 9, 12, 15 and 18 months of age and compared with the protective thresholds established in Kenyan children. Antibody titres were below the protective thresholds throughout the study period and we did not find any association with protection against febrile malaria. Antibodies to AMA1 and MSP1-19 appeared to be markers of exposure in the univariate analysis (and so associated with increasing risk) and adjusting for exposure reduced the strength and significance of this association. The antibody levels we measured are unlikely to be responsible for the apparent protection against febrile malaria seen in young infants. Further work to identify protective antibody responses might include functional assays and a wider range of antigens.