一种人源单克隆抗体可阻断疟疾传播，并确定了配子上一个高度保守的中和表位。
A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
作者信息
Coelho Camila H, Tang Wai Kwan, Burkhardt Martin, Galson Jacob D, Muratova Olga, Salinas Nichole D, Alves E Silva Thiago Luiz, Reiter Karine, MacDonald Nicholas J, Nguyen Vu, Herrera Raul, Shimp Richard, Narum David L, Byrne-Steele Miranda, Pan Wenjing, Hou Xiaohong, Brown Brittany, Eisenhower Mary, Han Jian, Jenkins Bethany J, Doritchamou Justin Y A, Smelkinson Margery G, Vega-Rodríguez Joel, Trück Johannes, Taylor Justin J, Sagara Issaka, Healy Sara A, Renn Jonathan P, Tolia Niraj H, Duffy Patrick E
机构信息
Pathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
出版信息
Nat Commun. 2021 Mar 19;12(1):1750. doi: 10.1038/s41467-021-21955-1.
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.
消除疟疾需要能够阻断寄生虫传播的工具。在此，我们对马里成年人接种富含半胱氨酸的230 kDa配子表面蛋白Pfs230（恶性疟原虫有性阶段发育中的关键蛋白）第一结构域疫苗后的B细胞受体反应进行了表征。在我们产生的9种Pfs230人单克隆抗体（mAb）中，有一种以补体依赖的方式有效阻断向蚊子的传播，并与配子表面发生反应；其他8种仅表现出低阻断活性或无阻断活性。与疫苗抗原结合的阻断传播的mAb的结构揭示了一个大的不连续构象表位，该表位对Pfs230的结构域1具有特异性，由该蛋白中的六个结构元件组成。该表位是保守的，表明阻断传播的mAb具有广泛的功能。这项研究为改进疟疾疫苗和开发用于消除疟疾的治疗性抗体提供了合理依据。
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