8VS8

Crystal structure of ADI-19425 Fab in complex with anti-idiotypic 1D3 Fab

8VS8 の概要

• エントリーDOI: 10.2210/pdb8vs8/pdb
• 分子名称: ADI-19425 Heavy Chain, ADI-19425 Light Chain, 1D3 Light Chain, ... (5 entities in total)
• 機能のキーワード: rsv, antibody, anti-idiotype, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 32
• 化学式量合計: 757465.02

構造登録者

Kher, G.,Homad, L.J.,McGuire, A.T.,Pancera, M. (登録日: 2024-01-23, 公開日: 2024-09-18, 最終更新日: 2026-04-01)

主引用文献

Scharffenberger, S.C.,Wan, Y.H.,Homad, L.J.,Kher, G.,Haynes, A.M.,Poudel, B.,Sinha, I.R.,Aldridge, N.,Pai, A.,Bibby, M.,Chhan, C.B.,Davis, A.R.,Moodie, Z.,Palacio, M.B.,Escolano, A.,McElrath, M.J.,Boonyaratanakornkit, J.,Pancera, M.,McGuire, A.T.
Targeting RSV-neutralizing B cell receptors with anti-idiotypic antibodies.
Cell Rep, 43:114811-114811, 2024

PubMed Abstract: Respiratory syncytial virus (RSV) causes lower respiratory tract infections with significant morbidity and mortality at the extremes of age. Vaccines based on the viral fusion protein are approved for adults over 60, but infant protection relies on passive immunity via antibody transfer or maternal vaccination. An infant vaccine that rapidly elicits protective antibodies would fulfill a critical unmet need. Antibodies arising from the VH3-21/VL1-40 gene pairing can neutralize RSV without the need for affinity maturation, making them attractive to target through vaccination. Here, we develop an anti-idiotypic monoclonal antibody (ai-mAb) immunogen that is specific for unmutated VH3-21/VL1-40 B cell receptors (BCRs). The ai-mAb efficiently engages B cells with bona fide target BCRs and does not activate off-target non-neutralizing B cells, unlike recombinant pre-fusion (preF) protein used in current RSV vaccines. These results establish proof of concept for using an ai-mAb-derived vaccine to target B cells hardwired to produce RSV-neutralizing antibodies.

PubMed: 39383036
DOI: 10.1016/j.celrep.2024.114811

実験手法

X-RAY DIFFRACTION (2.67 Å)