8Q5D

PfRH5 bound to monoclonal antibody MAD10-466

8Q5D の概要

• エントリーDOI: 10.2210/pdb8q5d/pdb
• 分子名称: Reticulocyte-binding protein homolog 5, Monoclonal antibody MAD10-466 heavy chain, Monoclonal antibody MAD10-466 light chain (3 entities in total)
• 機能のキーワード: plasmodium falciparum; monoclonal antibody; pfrh5; erythrocyte invasion, cell adhesion
• 由来する生物種: Plasmodium falciparum 3D7; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 175799.26

構造登録者

Farrell, B.,Higgins, M.K. (登録日: 2023-08-08, 公開日: 2024-06-05, 最終更新日: 2024-12-18)

主引用文献

Wang, L.T.,Cooper, A.J.R.,Farrell, B.,Miura, K.,Diouf, A.,Muller-Sienerth, N.,Crosnier, C.,Purser, L.,Kirtley, P.J.,Maciuszek, M.,Barrett, J.R.,McHugh, K.,Ogwang, R.,Tucker, C.,Li, S.,Doumbo, S.,Doumtabe, D.,Pyo, C.W.,Skinner, J.,Nielsen, C.M.,Silk, S.E.,Kayentao, K.,Ongoiba, A.,Zhao, M.,Nguyen, D.C.,Lee, F.E.,Minassian, A.M.,Geraghty, D.E.,Traore, B.,Seder, R.A.,Wilder, B.K.,Crompton, P.D.,Wright, G.J.,Long, C.A.,Draper, S.J.,Higgins, M.K.,Tan, J.
Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5.
Cell, 187:4981-4995.e14, 2024

PubMed Abstract: Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

PubMed: 39059381
DOI: 10.1016/j.cell.2024.06.037

実験手法

X-RAY DIFFRACTION (3.2 Å)