A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
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DOI：
10.1038/s41467-021-21955-1
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发表时间：
2021-03-19
影响因子：
16.6
通讯作者：
Duffy PE
中科院分区：
文献类型：
--
作者：
Coelho CH;Tang WK;Burkhardt M;Galson JD;Muratova O;Salinas ND;Alves E Silva TL;Reiter K;MacDonald NJ;Nguyen V;Herrera R;Shimp R;Narum DL;Byrne-Steele M;Pan W;Hou X;Brown B;Eisenhower M;Han J;Jenkins BJ;Doritchamou JYA;Smelkinson MG;Vega-Rodríguez J;Trück J;Taylor JJ;Sagara I;Healy SA;Renn JP;Tolia NH;Duffy PE
消除疟疾需要阻断寄生虫传播的工具。在这里，我们描述了马里成年人接种富含半胱氨酸的230 kDa配子表面蛋白Pfs230的第一结构域的B细胞受体反应，Pfs230是恶性疟原虫性发育阶段的关键蛋白。在我们制备的9种Pfs230人单克隆抗体（mab）中，一种以互补依赖的方式有效阻止传播到蚊子，并对配子表面起反应；其他8个只有低阻断活性或没有阻断活性。该传递阻断单抗与疫苗抗原复合物的结构揭示了一个大的不连续构象表位，特异于Pfs230的结构域1，包含蛋白中的6个结构元件。表位是保守的，这表明这种传递阻断单抗具有广泛的功能。本研究为改进疟疾疫苗和研制消除疟疾的治疗性抗体提供了合理依据。阻断疟疾传播的疫苗将是消除疟疾的重要工具。在这里，作者从接种了Pfs230疫苗的个体中鉴定出一种人单克隆抗体，该抗体以互补依赖的方式阻断恶性疟原虫向蚊子的传播，并与配子表面发生反应。
Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination. Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.
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影响因子：
46.9
作者：
Han, Arnold;Glanville, Jacob;Hansmann, Leo;Davis, Mark M.
通讯作者：
Davis, Mark M.
影响因子：
1.3
作者：
COLLINS, WE;WARREN, M;KEARSE, TS
通讯作者：
KEARSE, TS
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444906029799
发表时间：
2006-10-01
影响因子：
2.2
作者：
Aricescu, A. Radu;Lu, Weixian;Jones, E. Yvonne
通讯作者：
Jones, E. Yvonne
影响因子：
15.9
作者：
Healy，Sara A.;Anderson，Charles;Duffy，Patrick E.
通讯作者：
Duffy，Patrick E.