ジャーナル: J Infect / 年: 2023 タイトル: Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys. 著者: Craig Fenwick / Priscilla Turelli / Yoan Duhoo / Kelvin Lau / Cécile Herate / Romain Marlin / Myriam Lamrayah / Jérémy Campos / Line Esteves-Leuenberger / Alex Farina / Charlène Raclot / ...著者: Craig Fenwick / Priscilla Turelli / Yoan Duhoo / Kelvin Lau / Cécile Herate / Romain Marlin / Myriam Lamrayah / Jérémy Campos / Line Esteves-Leuenberger / Alex Farina / Charlène Raclot / Vanessa Genet / Flurin Fiscalini / Julien Cesborn / Laurent Perez / Nathalie Dereuddre-Bosquet / Vanessa Contreras / Kyllian Lheureux / Francis Relouzat / Rana Abdelnabi / Pieter Leyssen / Yves Lévy / Florence Pojer / Roger Le Grand / Didier Trono / Giuseppe Pantaleo / 要旨: OBJECTIVES: Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic ...OBJECTIVES: Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. 手法: Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 ...手法: Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. RESULTS: The P4J15 mAb shows <20 ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. CONCLUSIONS: The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations.
タンパク質・ペプチド: P4J15 Fragment Antigen-Binding Heavy Chain
タンパク質・ペプチド: P4J15 Fragment Antigen-Binding Light Chain
タンパク質・ペプチド: Spike protein S2'
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
-
超分子 #1: Spike XBB.1 RBD up - P4J15 Fab (local)
超分子
名称: Spike XBB.1 RBD up - P4J15 Fab (local) / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 詳細: local refinement from the Full XBB.1 spike and RBD complex.
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)
分子量
理論値: 72 kDa/nm
-
分子 #1: P4J15 Fragment Antigen-Binding Heavy Chain
分子
名称: P4J15 Fragment Antigen-Binding Heavy Chain / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO