8DFI

Crystal structure of moderately neutralizing / interfering human monoclonal antibody 42C11 Fab in complex with MSP1-19

8DFI の概要

• エントリーDOI: 10.2210/pdb8dfi/pdb
• 分子名称: Merozoite surface protein 1, 42C11 Fab Heavy Chain, 42C11 Fab Light Chain, ... (4 entities in total)
• 機能のキーワード: merozoite surface protein 1 (msp1), antigen-antibody complex, antigenic diversion, plasmodium falciparum, structural protein-immune system complex, structural protein/immune system
• 由来する生物種: Plasmodium falciparum 3D7; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 60667.67

構造登録者

Patel, P.N.,Tang, W.K.,Tolia, N.H. (登録日: 2022-06-22, 公開日: 2022-10-12, 最終更新日: 2024-10-23)

主引用文献

Patel, P.N.,Dickey, T.H.,Hopp, C.S.,Diouf, A.,Tang, W.K.,Long, C.A.,Miura, K.,Crompton, P.D.,Tolia, N.H.
Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion.
Nat Commun, 13:5888-5888, 2022

PubMed Abstract: Defining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria vaccine antigen and antibodies to MSP-1 are associated with protection from disease. However, MSP-1-based vaccines performed poorly in clinical trials in part due to a limited understanding of the protective antibody response to MSP-1 and of immune evasion by antigenic diversion. Antigenic diversion was identified as a mechanism wherein parasite neutralization by a MSP-1-specific rodent antibody was disrupted by MSP-1-specific non-inhibitory blocking/interfering antibodies. Here, we investigated a panel of MSP-1-specific naturally acquired human monoclonal antibodies (hmAbs). Structures of multiple hmAbs with diverse neutralizing potential in complex with MSP-1 revealed the epitope of a potent strain-transcending hmAb. This neutralizing epitope overlaps with the epitopes of high-affinity non-neutralizing hmAbs. Strikingly, the non-neutralizing hmAbs outcompete the neutralizing hmAb enabling parasite survival. These findings demonstrate the structural and mechanistic basis for a generalizable pathogen immune evasion mechanism through neutralizing and interfering human antibodies elicited by antigenic diversion, and provides insights required to develop potent and durable malaria interventions.

PubMed: 36202833
DOI: 10.1038/s41467-022-33336-3

実験手法

X-RAY DIFFRACTION (1.9 Å)