Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies.
Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies.
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DOI：
10.1016/j.immuni.2017.11.007
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发表时间：
2017-12-19
期刊：
影响因子：
32.4
通讯作者：
Wardemann H
中科院分区：
文献类型：
--
作者：
Triller G;Scally SW;Costa G;Pissarev M;Kreschel C;Bosch A;Marois E;Sack BK;Murugan R;Salman AM;Janse CJ;Khan SM;Kappe SHI;Adegnika AA;Mordmüller B;Levashina EA;Julien JP;Wardemann H
针对恶性疟原虫（Pf）子孢子的主要表面抗原环子孢子蛋白（CSP）的NANP重复序列的抗体可以在动物模型中保护免受疟疾，但难以在人类中诱导。在这里，我们克隆和表征罕见的亲和力成熟的人NANP反应性记忆B细胞抗体引起的天然Pf暴露，有效地抑制寄生虫在体内的传播和发展。我们揭示了抗体与NANP重复序列中两个不同保护性表位结合的分子细节。NANP重复识别主要由种系编码和免疫球蛋白（IG）重链互补决定区3（HCDR 3）残基介导，而亲和力成熟主要有助于稳定抗原结合位点构象。结合起来，我们的研究结果说明了探索人类抗CSP抗体反应的力量，以开发哺乳动物和蚊子载体中的疟疾控制工具，并为下一代CSP疟疾疫苗的基于结构的设计提供分子基础。
Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models, but are difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and Immunoglobulin (Ig) heavy chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines.
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影响因子：
64.5
作者：
Briney, Bryan;Sok, Devin;Jardine, Joseph G.;Kulp, Daniel W.;Skog, Patrick;Menis, Sergey;Jacak, Ronald;Kalyuzhniy, Oleksandr;de Val, Natalia;Sesterhenn, Fabian;Le, Khoa M.;Ramos, Alejandra;Jones, Meaghan;Saye-Francisco, Karen L.;Blane, Tanya R.;Spencer, Skye;Georgeson, Erik;Hu, Xiaozhen;Ozorowski, Gabriel;Adachi, Yumiko;Kubitz, Michael;Sarkar, Anita;Wilson, Ian A.;Ward, Andrew B.;Nemazee, David;Burton, Dennis R.;Schief, William R.
通讯作者：
Schief, William R.
影响因子：
6.7
作者：
Fisher, Camilla R.;Sutton, Henry J.;Cockburn, Ian A.
通讯作者：
Cockburn, Ian A.
影响因子：
64.5
作者：
de Taeye SW;Ozorowski G;Torrents de la Peña A;Guttman M;Julien JP;van den Kerkhof TL;Burger JA;Pritchard LK;Pugach P;Yasmeen A;Crampton J;Hu J;Bontjer I;Torres JL;Arendt H;DeStefano J;Koff WC;Schuitemaker H;Eggink D;Berkhout B;Dean H;LaBranche C;Crotty S;Crispin M;Montefiori DC;Klasse PJ;Lee KK;Moore JP;Wilson IA;Ward AB;Sanders RW
通讯作者：
Sanders RW
影响因子：
82.9
作者：
Ishizuka, Andrew S.;Lyke, Kirsten E.;Seder, Robert A.
通讯作者：
Seder, Robert A.
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