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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DOI：
10.1038/s41467-022-33379-6
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发表时间：
2022-09-24
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
有效的疟疾疫苗仍然是全球卫生优先事项，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。配子表面蛋白Pfs48/45是最有希望被纳入传播阻断疟疾疫苗的候选蛋白之一，它对蚊子中肠中寄生虫的发育至关重要。事实上，结合Pfs48/45的抗体如果作为蚊子血液的一部分与寄生虫一起摄入，可以防止传播。在这里，我们展示了全长Pfs48/45的结构，它的三个结构域形成了一个动态的、平面的、三角形的排列。我们揭示了传递阻断抗体和非阻断抗体结合Pfs48/45的位置。最后，我们证明了通过该分子结合的抗体可以阻断传递。这些研究将指导未来基于pfs48 /45的疫苗免疫原的开发。恶性疟原虫（Plasmodium falciparum）表面蛋白Pfs48/45是一种很有前途的抗疟疾候选疫苗，其结构尚未完全确定。在这里，作者介绍了全长分子的结构，并描述了传播阻断抗体的结合和活性。
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. Pfs48/45, a surface protein of Plasmodium falciparum, is a promising anti-malarial vaccine candidate whose structure is not entirely resolved. Here, the authors present the structure of the full-length molecule, and characterise the binding and activity of transmission blocking antibodies.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
3.7
作者：
Chowdhury DR;Angov E;Kariuki T;Kumar N
通讯作者：
Kumar N
影响因子：
6.1
作者：
Konarev, PV;Volkov, VV;Svergun, DI
通讯作者：
Svergun, DI
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
2.2
作者：
KUMAR, N
通讯作者：
KUMAR, N