荷兰医学微生物学系Matthijs M. Jore，Teun Bousema和加拿大病童医院研究所Jean-Philippe Julien共同合作，近期取得重要工作进展。他们研究发现高效天然获得的抗Pfs48/45人单克隆抗体阻断恶性疟原虫向蚊子的传播。相关研究成果2023年2月14日在线发表于《免疫学》杂志上。

据介绍，疟疾传播阻断疫苗（TBV）旨在诱导阻断疟疾寄生虫在蚊子体内发育的抗体，从而阻断进一步传播，并为疟疾控制和消除提供急需的工具。寄生虫表面蛋白Pfs48/45是主要的TBV候选蛋白。

研究人员从自然暴露于疟原虫的供体中分离并鉴定了一组81人Pfs48/45特异性单克隆抗体（mAb）。鉴定了针对Pfs48/45的三个结构域（D1–D3）中每一个的基因多样性mAb。最有效的mAb靶向D1和D3，在标准的膜进样试验中，分别以10和2μg/mL的浓度实现了>80%的传输减少活性。D3与四种不同mAb复合物的共晶体结构描绘了两个保守的保护性表位。

总之，这些Pfs48/45特异性人mAb提供了对保护性和非保护性表位的重要见解，可以进一步了解传播，并为设计改进的疟疾传播阻断疫苗候选物提供信息。

附：英文原文

Title: Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes

Author: Amanda Fabra-García, Sophia Hailemariam, Roos M. de Jong, Kirsten Janssen, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Danton Ivanochko, Anthony Semesi, Brandon McLeod, Martijn W. Vos, Marloes H.C. de Bruijni, Judith M. Bolscher, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Koen J. Dechering, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Jean-Philippe Julien, Matthijs M. Jore

Issue&Volume: 2023/02/14

Abstract: Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1–D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.

DOI: 10.1016/j.immuni.2023.01.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00019-5