7RD4

Crystal structure of PfCSP peptide 21 with vaccine-elicited human anti-malaria antibody m43.149

7RD4 の概要

• エントリーDOI: 10.2210/pdb7rd4/pdb
• 分子名称: antibody m43.149 heavy chain, antibody m43.149 light chain, Circumsporozoite protein, ... (4 entities in total)
• 機能のキーワード: malaria, csp, junction region, antibody, m43.149, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 106384.07

構造登録者

Xu, K.,Kwong, P.D. (登録日: 2021-07-09, 公開日: 2021-12-15, 最終更新日: 2024-10-23)

主引用文献

Kratochvil, S.,Shen, C.H.,Lin, Y.C.,Xu, K.,Nair, U.,Da Silva Pereira, L.,Tripathi, P.,Arnold, J.,Chuang, G.Y.,Melzi, E.,Schon, A.,Zhang, B.,Dillon, M.,Bonilla, B.,Flynn, B.J.,Kirsch, K.H.,Kisalu, N.K.,Kiyuka, P.K.,Liu, T.,Ou, L.,Pancera, M.,Rawi, R.,Reveiz, M.,Seignon, K.,Wang, L.T.,Waring, M.T.,Warner, J.,Yang, Y.,Francica, J.R.,Idris, A.H.,Seder, R.A.,Kwong, P.D.,Batista, F.D.
Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies.
Immunity, 54:2859-, 2021

PubMed Abstract: Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.

PubMed: 34788599
DOI: 10.1016/j.immuni.2021.10.017

実験手法

X-RAY DIFFRACTION (1.75 Å)