Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies

Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies
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候选疟疾疫苗 Pfs48/45 的结构及其传播阻断抗体的识别

DOI:
10.1101/2022.05.24.493318
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发表时间:
2022
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通讯作者:
Ko K
Ko K
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作者:
Ko K

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有效的疟疾疫苗仍然是全球卫生的优先事项,预防寄生虫传播的疫苗免疫原将在多组分疫苗中发挥重要作用。最有希望被纳入传播阻断疟疾疫苗的候选者之一是配子表面蛋白Pfs 48/45,这是蚊子中肠寄生虫发育所必需的。事实上,结合Pfs 48/45的抗体如果作为蚊子血粉的一部分与寄生虫一起摄入,可以防止传播。在这里,我们提出了全长Pfs 48/45的结构,显示其三个结构域形成一个动态的,平面的,三角形排列。我们揭示了在Pfs 48/45上结合的传播阻断和非阻断抗体。最后,我们证明了结合这种分子的抗体可以阻断传播。这些研究将指导未来基于Pfs 48/45的疫苗免疫原的开发。
An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.
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