Department of Immunology and Microbiology, Centre for Medical Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
PLoS One. 2020 Dec 17;15(12):e0243943. doi: 10.1371/journal.pone.0243943. eCollection 2020.
Developing a vaccine against Plasmodium falciparum malaria has been challenging, primarily due to high levels of antigen polymorphism and a complex parasite lifecycle. Immunization with the P. falciparum merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 has been shown to give rise to growth inhibitory and synergistic antisera. Therefore, these five merozoite proteins are considered to be promising candidates for a second-generation multivalent malaria vaccine. Nevertheless, little is known about IgG and IgM responses to these antigens in populations that are naturally exposed to P. falciparum. In this study, serum samples from clinically immune adults and malaria exposed children from Ghana were studied to compare levels of IgG and IgM specific for PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5. All five antigens were found to be specifically recognized by both IgM and IgG in serum from clinically immune adults and from children with malaria. Longitudinal analysis of the latter group showed an early, transient IgM response that was followed by IgG, which peaked 14 days after the initial diagnosis. IgG levels and parasitemia did not correlate, whereas parasitemia was weakly positively correlated with IgM levels. These findings show that IgG and IgM specific for merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 are high in children during P. falciparum malaria, but that the IgM induction and decline occurs earlier in infection than that of IgG.
开发针对恶性疟原虫疟疾的疫苗一直具有挑战性，主要是由于抗原高度多态性和寄生虫生命周期复杂。用恶性疟原虫裂殖体抗原 PfMSRP5、PfSERA9、PfRAMA、PfCyRPA 和 PfRH5 进行免疫接种已被证明可引起生长抑制和协同抗血清。因此，这五种裂殖体蛋白被认为是第二代多价疟疾疫苗的有前途的候选物。然而，对于自然暴露于恶性疟原虫的人群中针对这些抗原的 IgG 和 IgM 反应知之甚少。在这项研究中，研究了来自加纳具有临床免疫力的成年人和疟疾暴露儿童的血清样本，以比较针对 PfMSRP5、PfSERA9、PfRAMA、PfCyRPA 和 PfRH5 的 IgG 和 IgM 的特异性。在具有临床免疫力的成年人和患有疟疾的儿童的血清中，均发现所有五种抗原都被 IgM 和 IgG 特异性识别。对后者群体的纵向分析显示出早期短暂的 IgM 反应，随后是 IgG，在初次诊断后 14 天达到峰值。IgG 水平与寄生虫血症无相关性，而寄生虫血症与 IgM 水平呈弱正相关。这些发现表明，在恶性疟原虫疟疾期间，儿童体内针对裂殖体抗原 PfMSRP5、PfSERA9、PfRAMA、PfCyRPA 和 PfRH5 的 IgG 和 IgM 特异性很高，但 IgM 的诱导和下降发生在感染早期比 IgG 更早。
