Accumulation of Neutrophil Phagocytic Antibody Features Tracks With Naturally Acquired Immunity Against Malaria in Children.
Accumulation of Neutrophil Phagocytic Antibody Features Tracks With Naturally Acquired Immunity Against Malaria in Children.
复制标题
中性粒细胞吞噬抗体的积累具有儿童对疟疾的自然获得性免疫力。
DOI：
10.1093/infdis/jiad115
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Alter,Galit
中科院分区：
文献类型：
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作者：
Nziza,Nadege;Tran,TuanM;DeRiso,ElizabethA;Dolatshahi,Sepideh;Herman,JonathanD;deLacerda,Luna;Junqueira,Caroline;Lieberman,Judy;Ongoiba,Aissata;Doumbo,Safiatou;Kayentao,Kassoum;Traore,Boubacar;Crompton,PeterD;Alter,Galit
背景研究已经证明了抗体对疟疾的保护作用。众所周知，幼儿特别容易感染疟疾，这表明自然获得的临床免疫力会随着时间的推移而演变。然而，抗体功能的变化是否与自然获得性疟疾免疫力的获得相一致尚不完全清楚。方法利用系统血清学，我们对疟疾季节前未感染的马里儿童的子孢子和裂殖子特异性抗体谱进行了表征，这些儿童在恶性疟原虫（Pf）感染后控制寄生虫血症和发烧的能力存在差异。然后，我们评估了个体特征对总体临床结果的贡献，重点关注免疫显性子孢子 CSP 以及裂殖子 AMA1 和 MSP1 抗原。结果体液免疫随着年龄的增长而进化，其程度和功能质量都在扩大，特别是在血液阶段吞噬抗体活性方面。此外，就感染后的临床结果而言，受保护的儿童在疟疾季节之前具有较高的抗体依赖性中性粒细胞活性，以及较高水平的MSP1特异性IgG3和IgA以及CSP特异性IgG3和IgG4。结论这些数据表明功能性体液免疫随年龄的自然进化，并突出了与儿童疟疾控制相关的特定抗体Fc效应谱，为下一代疫苗或治疗方法的设计提供了线索。
BackgroundStudies have demonstrated the protective role of antibodies against malaria. Young children are known to be particularly vulnerable to malaria, pointing to the evolution of naturally acquired clinical immunity over time. However, whether changes in antibody functionality track with the acquisition of naturally acquired malaria immunity remains incompletely understood.MethodsUsing systems serology, we characterized sporozoite- and merozoite-specific antibody profiles of uninfected Malian children before the malaria season who differed in their ability to control parasitemia and fever followingPlasmodium falciparum(Pf) infection. We then assessed the contributions of individual traits to overall clinical outcomes, focusing on the immunodominant sporozoite CSP and merozoite AMA1 and MSP1 antigens.ResultsHumoral immunity evolved with age, with an expansion of both magnitude and functional quality, particularly within blood-stage phagocytic antibody activity. Moreover, concerning clinical outcomes postinfection, protected children had higher antibody-dependent neutrophil activity along with higher levels of MSP1-specific IgG3 and IgA and CSP-specific IgG3 and IgG4 prior to the malaria season.ConclusionsThese data point to the natural evolution of functional humoral immunity toPfwith age and highlight particular antibody Fc-effector profiles associated with the control of malaria in children, providing clues for the design of next-generation vaccines or therapeutics.