Assessing the functional impact of PfRh5 genetic diversity on ex vivo erythrocyte invasion inhibition.

Assessing the functional impact of PfRh5 genetic diversity on ex vivo erythrocyte invasion inhibition.
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DOI:
10.1038/s41598-021-81711-9
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发表时间:
2021-01-26
期刊:
影响因子:
4.6
通讯作者:
Bei AK
Bei AK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Moore AJ;Mangou K;Diallo F;Sene SD;Pouye MN;Sadio BD;Faye O;Mbengue A;Bei AK

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PfRh 5-Basigin配体-受体相互作用是裂殖子侵入过程中的重要步骤,并且代表了有吸引力的疫苗靶标。为了揭示PfRh 5的天然等位基因变体与侵袭抑制之间的基因型-表型关联,我们用靶向basigin的单克隆抗体结合PfRh 5下一代扩增子测序进行了离体侵袭抑制测定。我们发现,在所有测试的分离株的侵袭的剂量依赖性抑制,和任何单核苷酸多态性的侵袭抑制没有统计学上的显着差异。这项研究表明,即使在高度流行的环境中,PfRh 5仍然保持高度保守和功能上至关重要,支持继续开发作为菌株超越疟疾疫苗靶标。
The PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype–phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.
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