P. falciparum and P. vivax Orthologous Coiled-Coil Candidates for a Potential Cross-Protective Vaccine.

P. falciparum and P. vivax Orthologous Coiled-Coil Candidates for a Potential Cross-Protective Vaccine.
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恶性疟原虫和疟原虫直系同源卷曲圈候选物,用于潜在的交叉保护疫苗。

DOI:
10.3389/fimmu.2020.574330
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发表时间:
2020
影响因子:
7.3
通讯作者:
Agnolon V
Agnolon V
中科院分区:
医学2区
文献类型:
--
作者:
Ayadi I;Balam S;Audran R;Bikorimana JP;Nebie I;Diakité M;Felger I;Tanner M;Spertini F;Corradin G;Arevalo M;Herrera S;Agnolon V

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在过去四十年中,为研制疟疾疫苗作出了重大努力。尽管大多数努力都集中在恶性疟原虫疫苗的开发上,但目前寄生虫基因组、生物信息学工具以及用于重组和合成抗原生产的高通量系统的可用性有助于加速间日疟原虫疫苗的开发。我们之前在计算机上发现了几种含有α-螺旋螺旋基序的恶性疟原虫和间日疟原虫蛋白,这些蛋白代表了疫苗开发的新型推定抗原,因为它们具有高度的免疫原性,并且在许多体外功能测定中与保护有关。在这里,我们选择了5对恶性疟原虫和间日疟原虫的同源肽,使用在恶性疟原虫流行的非洲国家收集的血浆样本来评估它们的血清反应性。还研究了Pf-Pv交叉反应性。Pf27/Pv27、Pf43/Pv43和Pf45/Pv45是最有希望的交叉保护疫苗候选组合,因为它们在直接和竞争ELISA检测中表现出高度的识别,并且与各自的同源物具有交叉反应性。恶性疟原虫感染个体的血浆对间日疟原虫肽的识别表明这两种疟原虫之间存在高度的交叉反应性。设计结合这些表位的更长的多肽将允许在动物模型中评估其免疫原性和保护功效。
Over the last four decades, significant efforts have been invested to develop vaccines against malaria. Although most efforts are focused on the development of P. falciparum vaccines, the current availability of the parasite genomes, bioinformatics tools, and high throughput systems for both recombinant and synthetic antigen production have helped to accelerate vaccine development against the P. vivax parasite. We have previously in silico identified several P. falciparum and P. vivax proteins containing α-helical coiled-coil motifs that represent novel putative antigens for vaccine development since they are highly immunogenic and have been associated with protection in many in vitro functional assays. Here, we selected five pairs of P. falciparum and P. vivax orthologous peptides to assess their sero-reactivity using plasma samples collected in P. falciparum- endemic African countries. Pf-Pv cross-reactivity was also investigated. The pairs Pf27/Pv27, Pf43/Pv43, and Pf45/Pv45 resulted to be the most promising candidates for a cross-protective vaccine because they showed a high degree of recognition in direct and competition ELISA assays and cross-reactivity with their respective ortholog. The recognition of P. vivax peptides by plasma of P. falciparum infected individuals indicates the existence of a high degree of cross-reactivity between these two Plasmodium species. The design of longer polypeptides combining these epitopes will allow the assessment of their immunogenicity and protective efficacy in animal models.
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影响因子: 5.5
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