EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Cross-reactive sarbecovirus antibodies induced by mosaic RBD nanoparticles.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 21, Page e2501637122, Year 2025
掲載日	2025年5月27日
著者	Chengcheng Fan / Jennifer R Keeffe / Kathryn E Malecek / Alexander A Cohen / Anthony P West / Viren A Baharani / Annie V Rorick / Han Gao / Priyanthi N P Gnanapragasam / Semi Rho / Jaasiel Alvarez / Luisa N Segovia / Theodora Hatziioannou / Paul D Bieniasz / Pamela J Bjorkman /
PubMed 要旨	Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) ...Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) spike proteins that recognize SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles. Here, we describe neutralizing mAbs isolated from mosaic-8b-immunized rabbits, some on par with Pemgarda, the only currently FDA-approved therapeutic mAb. Deep mutational scanning, in vitro selection of spike resistance mutations, and single-particle cryo-electron microscopy structures of spike-antibody complexes demonstrated targeting of conserved RBD epitopes. Rabbit mAbs included critical D-gene segment RBD-recognizing features in common with human anti-RBD mAbs, despite rabbit genomes lacking an equivalent human D-gene segment, thus demonstrating that the immune systems of humans and other mammals can utilize different antibody gene segments to arrive at similar modes of antigen recognition. These results suggest that animal models can be used to elicit anti-RBD mAbs with similar properties to those raised in humans, which can then be humanized for therapeutic use, and that mosaic RBD nanoparticle immunization coupled with multiplexed screening represents an efficient way to generate and select broadly cross-reactive therapeutic pan-sarbecovirus and pan-SARS-CoV-2 variant mAbs.
リンク	Proc Natl Acad Sci U S A / PubMed:40402246
手法	EM (単粒子) / X線回折
解像度	2.4 - 3.5 Å
構造データ	48347 9ml4 EMDB-48347, PDB-9ml4: Structure of the SARS-CoV-2 Spike 6P in complex with the rabbit M8b-A10 Fab 手法: EM (単粒子) / 解像度: 3.3 Å 48348 9ml5 EMDB-48348, PDB-9ml5: Structure of the SARS-CoV-2 Spike 6P in complex with the rabbit M8b-B8 Fab 手法: EM (単粒子) / 解像度: 3.4 Å 48349 9ml6 EMDB-48349, PDB-9ml6: Structure of the SARS-CoV-2 Spike 6P in complex with the rabbit M8b-C9 Fab 手法: EM (単粒子) / 解像度: 3.5 Å 48350 9ml7 EMDB-48350, PDB-9ml7: Structure of the SARS-CoV-2 Spike 6P in complex with the rabbit M8b-C10 Fab 手法: EM (単粒子) / 解像度: 3.2 Å PDB-9ml8: Crystal structure of the SARS-CoV-2 RBD in complex with the rabbit M8b-B1 Fab 手法: X-RAY DIFFRACTION / 解像度: 2.4 Å PDB-9ml9: Crystal structure of the SARS-CoV-2 RBD in complex with the rabbit M8b-C9 Fab 手法: X-RAY DIFFRACTION / 解像度: 2.59 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-SO4: SULFATE ION / 硫酸ジアニオン ChemComp-HOH: WATER ChemComp-TRS: 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / トリス(ヒドロキシメチル)メチルアンモニウム / pH緩衝剤*YM
由来	severe acute respiratory syndrome coronavirus 2 (ウイルス) oryctolagus cuniculus (ウサギ)
キーワード	VIRAL PROTEIN/IMMUNE SYSTEM / immune system / neutralizing antibody / IMMUNE SYSTEM-VIRAL PROTEIN complex / VIRAL PROTEIN-IMMUNE SYSTEM complex