The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria.
The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria.
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DOI：
10.1038/srep33094
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发表时间：
2016-09-08
影响因子：
4.6
通讯作者：
Beeson JG
中科院分区：
文献类型：
--
作者：
Weaver R;Reiling L;Feng G;Drew DR;Mueller I;Siba PM;Tsuboi T;Richards JS;Fowkes FJI;Beeson JG
了解人类对疟疾免疫的靶点和机制对于促进疟疾监测的高效疫苗和血清学工具的开发具有重要意义。PfRH5和PfRipr蛋白在恶性疟原虫裂殖子的表面上形成复合物，其对于红细胞的侵入是必需的并且是疫苗候选物。我们确定了巴布亚新几内亚疟疾暴露个体对这些蛋白质的IgG亚类反应，以及它们与儿童纵向队列中疟疾保护的相关性。嗜细胞亚类，IgG1和IgG3，占主导地位，有限的IgG2和IgG4，和IgG亚类特异性反应较高的年龄较大的儿童和活动性感染。在调整潜在混杂因素后，PfRH5和PfRipr的高IgG3与疟疾风险降低显著且强烈相关，而IgG1应答的相关性通常较弱且无统计学显著性。结果进一步表明，疟疾暴露导致PfRH5和PfRipr以及其他PfRH侵入配体PfRH2和PfRH4的IgG 1和IgG 3的共获得。这些发现表明，IgG3对PfRH5和PfRipr的应答可能在介导天然获得性免疫中发挥重要作用，并支持其作为疫苗候选物的潜力及其作为免疫的抗体生物标志物的用途。
Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
17.1
作者：
Osier FH;Mackinnon MJ;Crosnier C;Fegan G;Kamuyu G;Wanaguru M;Ogada E;McDade B;Rayner JC;Wright GJ;Marsh K
通讯作者：
Marsh K
影响因子：
4
作者：
Baum, Jake;Chen, Lin;Cowman, Alan F.
通讯作者：
Cowman, Alan F.
影响因子：
3.1
作者：
Osier, Faith H. A.;Fegan, Gregory;Marsh, Kevin
通讯作者：
Marsh, Kevin
影响因子：
2.2
作者：
Marsh, K;Kinyanjui, S
通讯作者：
Kinyanjui, S