Vaccination with conserved regions of erythrocyte-binding antigens induces neutralizing antibodies against multiple strains of Plasmodium falciparum.

Vaccination with conserved regions of erythrocyte-binding antigens induces neutralizing antibodies against multiple strains of Plasmodium falciparum.
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DOI:
10.1371/journal.pone.0072504
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Cowman AF
Cowman AF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Healer J;Thompson JK;Riglar DT;Wilson DW;Chiu YH;Miura K;Chen L;Hodder AN;Long CA;Hansen DS;Baum J;Cowman AF

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一种针对恶性疟疾的高效疫苗应该会产生强大的、超越免疫力的菌株,从而广泛保护人们免受全球流行的各种寄生虫的侵袭。我们的目标是确定符合标准的候选疫苗。我们测量了针对一系列抗原的抗体的生长抑制活性,以确定哪些抗体可以有效地阻止恶性疟原虫不同地理株的裂殖子入侵。这表明恶性疟原虫红细胞结合抗原(EBA)-175的保守区域III-V能够诱导抗体,有效地抑制裂殖子在不同寄生虫株之间的入侵,包括那些依赖于独立于EBA-175功能的入侵途径的抗体。此外,EBA-140保守的RIII-V结构域在体外也能诱导出具有很强的寄生虫生长抑制活性的抗体。我们确定了EBA-175的一个替代的高度保守的区域(RIV-V),它存在于所有EBA蛋白中,是有效的、超越中和抗体的菌株的靶标,代表了作为疟疾疫苗成分开发的一个强有力的候选者。
A highly effective vaccine against Plasmodium falciparum malaria should induce potent, strain transcending immunity that broadly protects against the diverse population of parasites circulating globally. We aimed to identify vaccine candidates that fulfill the criteria. We have measured growth inhibitory activity of antibodies raised to a range of antigens to identify those that can efficiently block merozoite invasion for geographically diverse strains of P. falciparum. This has shown that the conserved Region III-V, of the P. falciparum erythrocyte-binding antigen (EBA)-175 was able to induce antibodies that potently inhibit merozoite invasion across diverse parasite strains, including those reliant on invasion pathways independent of EBA-175 function. Additionally, the conserved RIII-V domain of EBA-140 also induced antibodies with strong in vitro parasite growth inhibitory activity. We identify an alternative, highly conserved region (RIV-V) of EBA-175, present in all EBA proteins, that is the target of potent, strain transcending neutralizing antibodies, that represents a strong candidate for development as a component in a malaria vaccine.
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