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Pfs230 域7 是一个强大的疟疾传播阻断单克隆抗体的目标

Maartje R Inklaar¹, Roos M de Jong¹, Ezra T Bekkering¹

¹Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.

|December 12, 2023

概括

新的疟疾传播阻断疫苗 (TBV) 针对Pfs230领域7. 一种新型抗体有效地阻止了寄生虫的传播,通过诱导蚊子体内的配体依赖性雌激素溶解.

科学领域:

免疫学免疫学免疫学
寄生虫学的寄生虫学
疫苗开发疫苗开发

背景情况:

阻止疟疾传播的疫苗 (TBVs) 旨在防止蚊子中的虫寄生虫的发展.
Pfs230的Pro-domain和第一个6-Cysteine域 (Pro-D1) 是已知的目标,但其他功能域仍然未被发现.

研究的目的:

为了在Pfs230蛋白中确定阻断传播抗体的新功能标.
开发和评估Pfs230域7向抗体的传播阻断能力.

主要方法:

产生了一种针对Pfs230域7的小鼠单克隆抗体 (mAb) 18F25.1.
通过使用CRISPR/Cas9.2a设计了一个子类切换的补充固定变体 (mAb 18F25.2a).
通过膜养试验评估了伴生体溶解和寄生虫传播的减少.

主要成果:

mAb 18F25.1被确定为针对 Pfs230 域 7.
设计的mAb 18F25.2a诱导了Plasmodium雌性性体的体外溶解.
mAb 18F25.2a 显著减少了 Anopheles stephensi 蚊子感染,以一种依赖补剂的方式.

结论:

Pfs230 域7 是疟疾传播阻断抗体的新功能标.
这一发现支持探索超出Pro-D1的Pfs230域,用于TBV发育.
开发的补体固定抗体表现出强大的传播阻断活性.

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