当前位置: X-MOL 学术PLOS Pathog. › 论文详情
Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein
PLoS Pathogens ( IF 6.463 ) Pub Date : 2020-03-09 , DOI: 10.1371/journal.ppat.1008373
David Oyen; Jonathan L. Torres; Phillip C. Aoto; Yevel Flores-Garcia; Spela Binter; Tossapol Pholcharee; Sean Carroll; Sini Reponen; Rachael Wash; Qi Liang; Franck Lemiale; Emily Locke; Allan Bradley; C. Richter King; Daniel Emerling; Paul Kellam; Fidel Zavala; Andrew B. Ward; Ian A. Wilson

Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection.
更新日期:2020-03-10

 

全部期刊列表>>
智控未来
聚焦商业经济政治法律
跟Nature、Science文章学绘图
控制与机器人
招募海内外科研人才,上自然官网
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
x-mol收录
湖南大学化学化工学院刘松
上海有机所
李旸
南方科技大学
西湖大学
伊利诺伊大学香槟分校
徐明华
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug