A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens.
A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens.
复制标题
DOI：
10.1186/s12916-016-0691-6
复制
发表时间：
2016-09-23
期刊：
影响因子：
9.3
通讯作者：
Beeson JG
中科院分区：
文献类型：
--
作者：
Drew DR;Wilson DW;Elliott SR;Cross N;Terheggen U;Hodder AN;Siba PM;Chelimo K;Dent AE;Kazura JW;Mueller I;Beeson JG
许多疟疾候选疫苗的多态性对获得高效疫苗提出了重大挑战。目前，人们对多态性候选疫苗在人群中的流行率和功能性免疫应答模式知之甚少，无法指导疫苗设计。针对血液期恶性疟原虫的主要多态性候选疫苗是顶端膜抗原1（AMA 1），其对于红细胞侵入是必需的。AMA 1作为获得性人抑制性抗体的靶标的重要性、其等位基因特异性和在人群中的流行率尚不清楚，但对于疫苗设计至关重要。表达不同AMA 1等位基因的恶性疟原虫株系被基因工程化，并用于定量来自成人和儿童两个疟疾暴露人群的功能性抗体。AMA 1抗体的收购也检测使用酶联免疫吸附试验（ELISA）和竞争ELISA（使用不同的AMA 1等位基因）从相同的人群。我们发现AMA 1是自然获得的侵袭抑制抗体的主要靶点，这些抗体在疟疾流行人群中非常普遍，并显示出高度的等位基因特异性。值得注意的是，不同等位基因的抑制性抗体的患病率在人群内和地理位置之间差异很大。针对三种特定等位基因的抑制性抗体非常普遍（巴布亚新几内亚的FVO和W2 mef;肯尼亚的FVO和XIE），确定了它们的潜在疫苗纳入。通过标准或竞争ELISA测量抗体并不能强烈预测等位基因特异性抑制抗体。用我们的新测定法检测的等位基因特异性功能性抗体应答的模式可能表明，获得性免疫是针对在每个地理位置流行的血清型引起的。这些发现提供了新的见解的性质和收购的多态性候选疫苗和战略，以量化人群中的功能性免疫，以指导合理的疫苗设计的功能性免疫。本文的在线版本（doi：10.1186/s12916-016-0691-6）包含补充材料，可供授权用户使用。
The polymorphic nature of many malaria vaccine candidates presents major challenges to achieving highly efficacious vaccines. Presently, there is very little knowledge on the prevalence and patterns of functional immune responses to polymorphic vaccine candidates in populations to guide vaccine design. A leading polymorphic vaccine candidate against blood-stage Plasmodium falciparum is apical membrane antigen 1 (AMA1), which is essential for erythrocyte invasion. The importance of AMA1 as a target of acquired human inhibitory antibodies, their allele specificity and prevalence in populations is unknown, but crucial for vaccine design. P. falciparum lines expressing different AMA1 alleles were genetically engineered and used to quantify functional antibodies from two malaria-exposed populations of adults and children. The acquisition of AMA1 antibodies was also detected using enzyme-linked immunosorbent assay (ELISA) and competition ELISA (using different AMA1 alleles) from the same populations. We found that AMA1 was a major target of naturally acquired invasion-inhibitory antibodies that were highly prevalent in malaria-endemic populations and showed a high degree of allele specificity. Significantly, the prevalence of inhibitory antibodies to different alleles varied substantially within populations and between geographic locations. Inhibitory antibodies to three specific alleles were highly prevalent (FVO and W2mef in Papua New Guinea; FVO and XIE in Kenya), identifying them for potential vaccine inclusion. Measurement of antibodies by standard or competition ELISA was not strongly predictive of allele-specific inhibitory antibodies. The patterns of allele-specific functional antibody responses detected with our novel assays may indicate that acquired immunity is elicited towards serotypes that are prevalent in each geographic location. These findings provide new insights into the nature and acquisition of functional immunity to a polymorphic vaccine candidate and strategies to quantify functional immunity in populations to guide rational vaccine design. The online version of this article (doi:10.1186/s12916-016-0691-6) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
6.7
作者：
Collins, Christine R.;Withers-Martinez, Chrislaine;Hackett, Fiona;Blackman, Michael J.
通讯作者：
Blackman, Michael J.
自然感染和疫苗接种诱导的人类抗膜抗原-1抗体的生物学活性的比较。
DOI：
10.4049/jimmunol.181.12.8776
发表时间：
2008-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Miura K;Zhou H;Moretz SE;Diouf A;Thera MA;Dolo A;Doumbo O;Malkin E;Diemert D;Miller LH;Mullen GE;Long CA
通讯作者：
Long CA
影响因子：
3.6
作者：
Healer, J;Murphy, V;Batchelor, A
通讯作者：
Batchelor, A
影响因子：
3.7
作者：
Drew DR;Hodder AN;Wilson DW;Foley M;Mueller I;Siba PM;Dent AE;Cowman AF;Beeson JG
通讯作者：
Beeson JG
影响因子：
3.3
作者：
CATTANI, JA;TULLOCH, JL;CLANCY, R
通讯作者：
CLANCY, R