Analysis of the Diverse Antigenic Landscape of the Malaria Invasion Protein RH5 Identifies a Potent Vaccine-Induced Human Public Antibody Clonotype
Analysis of the Diverse Antigenic Landscape of the Malaria Invasion Protein RH5 Identifies a Potent Vaccine-Induced Human Public Antibody Clonotype
复制标题
疟疾侵袭蛋白 RH5 的多样化抗原图谱分析鉴定出一种有效的疫苗诱导的人类公共抗体克隆型
DOI：
10.1101/2023.10.04.560576
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Barrett J
中科院分区：
文献类型：
--
作者：
Barrett J
高度保守且必需的恶性疟原虫网织红细胞结合蛋白同源物 5 (PfRH5) 已成为疫苗的主要靶标，旨在预防引起疾病的血液期疟疾。然而，人类疫苗诱导的抗体反应的特征尚未明确，这种抗体反应能够高效抑制疟疾寄生虫侵入红细胞。在这里，我们表征了由最先进的 PfRH5 疫苗诱导的 200 多种人 IgG 单克隆抗体。我们定义了该分子的抗原图谱，并确定表位特异性、抗体关联率和 PfRH5 内抗体相互作用是功能性抗寄生虫效力的关键决定因素。此外，我们还鉴定了一种种系基因组合，该组合可产生一类异常有效的抗体，并证明其预防疟原虫的潜力。体内恶性疟原虫挑战。这个综合数据集提供了一个框架来指导合理设计下一代疫苗和预防性抗体，以预防血期疟疾。
The highly conserved and essentialPlasmodium falciparumreticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines that seek to protect against the disease-causing blood-stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here we characterize over 200 human IgG monoclonal antibodies induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule, and establish epitope specificity, antibody association rate and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect againstP. falciparumparasite challengein vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.
登录
查看更多内容
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.9
作者：
wwPDB consortium
通讯作者：
wwPDB consortium
PCRCR 复合物对于恶性疟原虫入侵人类红细胞至关重要。
影响因子：
28.3
作者：
通讯作者：
--
影响因子：
64.8
作者：
Wright, Katherine E.;Hjerrild, Kathryn A.;Bartlett, Jonathan;Douglas, Alexander D.;Jin, Jing;Brown, Rebecca E.;Illingworth, Joseph J.;Ashfield, Rebecca;Clemmensen, Stine B.;de Jongh, Willem A.;Draper, Simon J.;Higgins, Matthew K.
通讯作者：
Higgins, Matthew K.
影响因子：
64.8
作者：
Crosnier, Cecile;Bustamante, Leyla Y.;Bartholdson, S. Josefin;Bei, Amy K.;Theron, Michel;Uchikawa, Makoto;Mboup, Souleymane;Ndir, Omar;Kwiatkowski, Dominic P.;Duraisingh, Manoj T.;Rayner, Julian C.;Wright, Gavin J.
通讯作者：
Wright, Gavin J.