Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes.
Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes.
复制标题
针对 Pfs48/45 的高效、天然获得的人类单克隆抗体可阻止恶性疟原虫传播给蚊子。
DOI：
10.1016/j.immuni.2023.01.009
复制
发表时间：
2023-02-14
期刊：
影响因子：
32.4
通讯作者：
Jore, Matthijs M.
中科院分区：
文献类型：
--
作者：
Fabra-Garcia, Amanda;Hailemariam, Sophia;de Jong, Roos M.;Janssen, Kirsten;Teelen, Karina;van de Vegte-Bolmer, Marga;van Gemert, Geert-Jan;Ivanochko, Danton;Semesi, Anthony;McLeod, Brandon;Vos, Martijn W.;de Bruijni, Marloes H. C.;Bolscher, Judith M.;Szabat, Marta;Vogt, Stefanie;Kraft, Lucas;Duncan, Sherie;Kamya, Moses R.;Feeney, Margaret E.;Jagannathan, Prasanna;Greenhouse, Bryan;Dechering, Koen J.;Sauerwein, Robert W.;King, C. Richter;MacGill, Randall S.;Bousema, Teun;Julien, Jean-Philippe;Jore, Matthijs M.
疟疾传播阻断疫苗旨在诱导阻断疟原虫在蚊子体内发育的抗体，从而阻断进一步传播，并为控制和消除疟疾提供急需的工具。寄生虫表面蛋白Pfs48/45是主要的TBV候选者。在这里，我们从自然暴露于疟原虫的供体中分离并鉴定了81个人类pfs48 /45特异性单克隆抗体（mab）。鉴定了Pfs48/45的三个结构域（D1-D3）的遗传多样性单克隆抗体。最有效的单抗靶向D1和D3，在标准的膜进样实验中，分别在10和2 μg/mL的浓度下，达到80%的传质降低活性。D3与四种不同单克隆抗体复合物的共晶结构划定了两个保守的保护性表位。总之，这些pfs48 /45特异性的人单克隆抗体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候选疫苗提供信息。针对Pfs48/45结构域2的抗体具有低或无降低传播活性。针对结构域3的强效抗体针对两个保守的表位。疟原虫表面蛋白Pfs48/45是一种主要的传播阻断疫苗候选物，但对自然获得的针对该靶点的抗体的特异性知之甚少。Fabra-García等人从自然暴露的个体中分离并鉴定了81个人类单克隆抗体，并证明了最有效的抗体靶向Pfs48/45的结构域1和3。
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. Isolated 81 unique mAbs directed to Pfs48/45 elicited in naturally exposed individuals The most potent mAbs target domains 1 and 3 of Pfs48/45 Antibodies against domain 2 have low or no transmission-reducing activity Potent antibodies against domain 3 target two conserved epitopes The malaria parasite surface protein Pfs48/45 is a leading transmission-blocking vaccine candidate, but little is known about the specificity of naturally acquired antibodies against this target. Fabra-García et al. isolate and characterize a panel of 81 human monoclonal antibodies from naturally exposed individuals and demonstrate that the most potent antibodies target domains 1 and 3 of Pfs48/45.
登录
查看更多内容
影响因子：
32.4
作者：
McLeod, Brandon;Mabrouk, Moustafa T.;Miura, Kazutoyo;Ravichandran, Rashmi;Kephart, Sally;Hailemariam, Sophia;Pham, Thao P.;Semesi, Anthony;Kucharska, Iga;Kundu, Prasun;Huang, Wei-Chiao;Johnson, Max;Blackstone, Alyssa;Pettie, Deleah;Murphy, Michael;Kraft, John C.;Leaf, Elizabeth M.;Jiao, Yang;Van de Vegte-Bolmer, Marga;Van Gemert, Geert-Jan;Ramjith, Jordache;King, C. Richter;MacGill, Randall S.;Wu, Yimin;Lee, Kelly K.;Jore, Matthijs M.;King, Neil P.;Lovell, Jonathan F.;Julien, Jean-Philippe
通讯作者：
Julien, Jean-Philippe
影响因子：
16.6
作者：
Lennartz F;Brod F;Dabbs R;Miura K;Mekhaiel D;Marini A;Jore MM;Søgaard MM;Jørgensen T;de Jongh WA;Sauerwein RW;Long CA;Biswas S;Higgins MK
通讯作者：
Higgins MK
影响因子：
17.1
作者：
Jones BE;Brown-Augsburger PL;Corbett KS;Westendorf K;Davies J;Cujec TP;Wiethoff CM;Blackbourne JL;Heinz BA;Foster D;Higgs RE;Balasubramaniam D;Wang L;Zhang Y;Yang ES;Bidshahri R;Kraft L;Hwang Y;Žentelis S;Jepson KR;Goya R;Smith MA;Collins DW;Hinshaw SJ;Tycho SA;Pellacani D;Xiang P;Muthuraman K;Sobhanifar S;Piper MH;Triana FJ;Hendle J;Pustilnik A;Adams AC;Berens SJ;Baric RS;Martinez DR;Cross RW;Geisbert TW;Borisevich V;Abiona O;Belli HM;de Vries M;Mohamed A;Dittmann M;Samanovic MI;Mulligan MJ;Goldsmith JA;Hsieh CL;Johnson NV;Wrapp D;McLellan JS;Barnhart BC;Graham BS;Mascola JR;Hansen CL;Falconer E
通讯作者：
Falconer E
影响因子：
3.1
作者：
Duffy, PE;Kaslow, DC
通讯作者：
Kaslow, DC
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