Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates
Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates
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DOI：
10.1016/j.jinf.2015.03.007
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发表时间：
2015-07-01
影响因子：
28.2
通讯作者：
Bousema, Teun
中科院分区：
文献类型：
--
作者：
Jones, Sophie;Grignard, Lynn;Bousema, Teun
目的：Pfs48/45和Pfs230是恶性疟原虫有性期蛋白，是很有希望的疟疾传播阻断疫苗候选者。针对这些蛋白的抗体反应可能是自然获得的，目标抗原可能处于选择压力下。这将对未来自然疟疾暴露人群疫苗免疫原性和有效性的评估产生影响。方法：我们测定了加纳、坦桑尼亚和布基纳法索三个疟疾流行地区的儿童对重组蛋白Pfs48/45-10C和Pfs230-230CMB的自然获得性抗体应答。结果：10C抗体阳性率为1.1~18.2%，230CMB抗体阳性率为6.7~18.9%。在布基纳法索，我们观察到了10C(p<；0.001)和230CMB(p=0.031)的年龄相关习得模式的证据。在单独的数据集上的膜喂养分析表明，10C(p=0.017)和230CMB(p=0.049)的功能传递降低活性与抗体流行率之间存在关联。在126份样本中，pfs48/45有17个单核苷酸多态，在pfs48/45 10C区有5个非同义SNPs。结论：两种候选疫苗均存在天然获得性抗体反应，通过降低感染者的传播力而具有功能相关性。我们鉴定了pfs48/45的遗传多态，表现出地理特异性。(C)2015年英国感染协会。爱思唯尔有限公司出版。保留所有权利。
Objectives: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria.Methods: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45.Results: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region.Conclusions: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.