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首页> 外文期刊>Frontiers in Immunology >Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination
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Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination

机译:恶性疟原虫抗原相关的IgG亚类应答的不同模式与疟疾保护和RTS,S疫苗接种相关

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摘要

Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhi?a in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG _(1?4) responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI.
机译:对恶性疟原虫疟疾的天然获得性免疫(NAI)主要由IgG抗体介导,但尚未明确定义亚类,表位靶标和效应子功能。剖析介导NAI的抗体反应的类型和特异性是开发更有效的疫苗来控制该疾病的关键步骤。我们调查了疟疾抗原的IgG亚类在预防疾病中的作用以及影响其水平的因素,包括RTS,S / AS01E疫苗接种。我们在参加疟疾传播强度不同的两个地点的三个阶段的非洲儿童和婴儿中,分别在基线和初次接种RTS,S或比较品后1个月分析了血浆和血清样本:加纳的金塔姆坡和莫桑比克的曼希亚。我们使用定量悬浮阵列技术(qSAT)来测量对35恶性疟原虫红细胞前和血液阶段抗原的IgG _(1?4)反应。我们的结果表明,IgG反应模式主要是IgG1或IgG3,而IgG2和IgG4的水平较低。年龄,部位和RTS,S疫苗接种显着影响针对不同抗原的抗体亚类水平和对临床疟疾的易感性。单变量和多变量分析显示,与主要针对特定​​抗原的嗜细胞性IgG3水平保护相关,其次为IgG1水平,并且出乎意料的是,也与IgG4水平相关,主要与RTS,S疫苗接种后增加的抗原(例如MSP5和MSP1 Block 2)相关。 。相反,IgG2与疟疾风险相关。在RTS,S疫苗中进行的分层分析指出,在RTS,S疫苗接种后,IgG4反应与主要涉及促红细胞前抗原的免疫力之间存在新型关联。多标记分析显示IgG3应答对疟疾保护和IgG2应答对疟疾风险有重要贡献。我们建议,嗜细胞和非嗜性IgG抗体的模式是抗原依赖性的,并且比最初认为的更为复杂,并且两种类型的亚类的机制都可能参与保护。我们的数据还表明,NAS显着影响RTS,S的功效,并表明RTS,S疫苗接种会显着改变NAI。

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