National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI145687
米国
引用
ジャーナル: bioRxiv / 年: 2021 タイトル: The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates. 著者: Dapeng Li / Robert J Edwards / Kartik Manne / David R Martinez / Alexandra Schäfer / S Munir Alam / Kevin Wiehe / Xiaozhi Lu / Robert Parks / Laura L Sutherland / Thomas H Oguin / Charlene ...著者: Dapeng Li / Robert J Edwards / Kartik Manne / David R Martinez / Alexandra Schäfer / S Munir Alam / Kevin Wiehe / Xiaozhi Lu / Robert Parks / Laura L Sutherland / Thomas H Oguin / Charlene McDanal / Lautaro G Perez / Katayoun Mansouri / Sophie M C Gobeil / Katarzyna Janowska / Victoria Stalls / Megan Kopp / Fangping Cai / Esther Lee / Andrew Foulger / Giovanna E Hernandez / Aja Sanzone / Kedamawit Tilahun / Chuancang Jiang / Longping V Tse / Kevin W Bock / Mahnaz Minai / Bianca M Nagata / Kenneth Cronin / Victoria Gee-Lai / Margaret Deyton / Maggie Barr / Tarra Von Holle / Andrew N Macintyre / Erica Stover / Jared Feldman / Blake M Hauser / Timothy M Caradonna / Trevor D Scobey / Wes Rountree / Yunfei Wang / M Anthony Moody / Derek W Cain / C Todd DeMarco / ThomasN Denny / Christopher W Woods / Elizabeth W Petzold / Aaron G Schmidt / I-Ting Teng / Tongqing Zhou / Peter D Kwong / John R Mascola / Barney S Graham / Ian N Moore / Robert Seder / Hanne Andersen / Mark G Lewis / David C Montefiori / Gregory D Sempowski / Ralph S Baric / Priyamvada Acharya / Barton F Haynes / Kevin O Saunders 要旨: SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor- ...SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection , while five non-neutralizing NTD antibodies mediated FcγR-independent infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while antibody-enhanced infection does not necessarily herald enhanced infection , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.
全体 : Complex of RBD-directed Fab DH1042 with hexapro SARS-CoV-2 spike ...
全体
名称: Complex of RBD-directed Fab DH1042 with hexapro SARS-CoV-2 spike ectodomain
要素
複合体: Complex of RBD-directed Fab DH1042 with hexapro SARS-CoV-2 spike ectodomain
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超分子 #1: Complex of RBD-directed Fab DH1042 with hexapro SARS-CoV-2 spike ...
超分子
名称: Complex of RBD-directed Fab DH1042 with hexapro SARS-CoV-2 spike ectodomain タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: Fab fragment generated by proteolytic cleavage of IgG antibody
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)
組換発現
生物種: Homo sapiens (ヒト) / 組換細胞: 293F / 組換プラスミド: p-alpha-H
分子量
理論値: 481.8 KDa
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実験情報
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構造解析
手法
ネガティブ染色法
解析
単粒子再構成法
試料の集合状態
particle
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試料調製
濃度
0.1 mg/mL
緩衝液
pH: 7.4 構成要素:
濃度
式
名称
150.0 mM
NaCl
sodium chloride
20.0 mM
HEPES buffer
5.0 g/dL
glycerol
染色
タイプ: NEGATIVE / 材質: Uranyl Formate 詳細: Samples were diluted to 0.1 mg/mL in 20 mM HEPES buffer, pH 7.4, with 5% glycerol, 150 mM NaCl, and 7.5 mM glutaraldehyde. After 5 minute incubation at room temperature, sufficient 1 M Tris ...詳細: Samples were diluted to 0.1 mg/mL in 20 mM HEPES buffer, pH 7.4, with 5% glycerol, 150 mM NaCl, and 7.5 mM glutaraldehyde. After 5 minute incubation at room temperature, sufficient 1 M Tris stock, pH 7.4, was added to a final concentration of 75 mM Tris to quench unreacted glutaraldehyde, and was then incubated 5 minutes. Sample was then applied to a carbon film over 400 mesh copper EM grids that had been glow-discharged, incubated 1 minute, and then stained with 2% uranyl formate.
詳細: Map of PDB 6VSB was generated within Chimera using the molmap function at 15 Angstrom resolution and 4.02 Angstrom grid spacing. This map was low-pass filtered to 60 Angstrom before initiating refinements.