Structure and function analysis of a potent human neutralizing antibody CA521FALA against SARS-CoV-2

Song, Deyong; Wang, Wenbo; Dong, Chuangchuang; Zong, Ning; Liu, Xiu; Liu, Chuan; Du, Guangying; Sha, Chunjie; Wang, Kailin; Sun, Baiping; Zhao, Yanyan; Wang, Qiaoping; Xu, Hongguang; Li, Ying; Shen, Zhenduo; Jiao, Jie; Wang, Ruiying; Tian, Jingwei; Liu, Wanhui; Wang, Lan; Deng, Yong-Qiang; Dou, Changlin

doi:10.1038/s42003-021-02029-w

Cited by 12 publications

(11 citation statements)

References 37 publications

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“…In this study, the safety of a single-dose injection of LY-CovMab was as expected for a full-length recombinant human antibody in all five dose groups from 30 to 2400 mg [ 5 ]. We did not observe injection site reactions and hypersensitivity reactions, which have been reported in studies of other neutralizing antibodies [ 6 , 7 ].…”

Section: Discussionmentioning

confidence: 91%

“…Preclinically reported data from LY-CovMab effectively inhibiting pseudovirus and authentic virus infection in vitro and in vivo by interfering with the mechanism that the virus attaches to the host cell suggested that it could be a promising SARS-CoV-2 neutralizing antibody candidate [ 5 ]. Consistent with our preclinical finding, LY-CovMab displayed a good safety and pharmacokinetic profile in the first-in-human study, which supported its clinical potential.…”

Section: Discussionmentioning

confidence: 99%

“…LY-CovMab, developed by Shandong BoAn Biotechnology Co., Ltd., is a fully humanized monoclonal antibody manufactured by recombinant technology and used to counteract COVID-19 [ 5 ]. It belongs to the IgG4 subtype and consists of two heavy chains and two light chains with a molecular weight of approximately 147 kDa.…”

Section: Introductionmentioning

confidence: 99%

“…Structural analysis revealed that LY-CovMab recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 receptor-binding domain (RBD) in the spike protein. LY-CovMab blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously [ 5 ]. In preclinical study, a single-dose administration of LY-CovMab dramatically reduced RNA viral loads of BALB/c mice who received MAScp6 challenge and resulted in a 34,914-fold and 693-fold reduction of viral titers in the lungs and tracheas at 3 days post infection compared with a single-dose administration of phosphate-buffered saline [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…LY-CovMab blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously [ 5 ]. In preclinical study, a single-dose administration of LY-CovMab dramatically reduced RNA viral loads of BALB/c mice who received MAScp6 challenge and resulted in a 34,914-fold and 693-fold reduction of viral titers in the lungs and tracheas at 3 days post infection compared with a single-dose administration of phosphate-buffered saline [ 5 ]. Furthermore, LY-CovMab has demonstrated a good pharmacokinetic profile following a single-dose intravascular injection in mice and rhesus monkeys [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2

et al. 2021

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Introduction We aimed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of LY-CovMab in Chinese healthy adults. Methods We conducted a phase 1, randomized, dose-escalation, placebo-controlled trial in 42 volunteers, 18–45 years of age, and 40 out of 42 received a single dose of LY-CovMab or placebo with LY-CovMab at a dose of 30 mg, 150 mg, 600 mg, 1200 mg, and 2400 mg. There were ten subjects in each group receiving LY-CovMab or placebo in a 4:1 ratio with the exception that the 30 mg group had two subjects both receiving LY-CovMab. Results Among the 42 randomized participants, 40 received an injection with 32 administered LY-CovMab and 8 administered placebo. A total of 18 drug-related treatment-emergent adverse events (TEAEs) were reported in 12 subjects (30.0%), including protein urine present (25%, 10/40) and blood creatinine increased (7.5%, 3/40). The incidence of drug-related TEAE in each dosage group was as follows: 150 mg (28.6%, 2/7), 600 mg (25%, 2/8), 1200 mg (14.3%, 1/7), 2400 mg (50%, 4/8), and placebo (37.5%, 3/8). All drug-related TEAEs were grade 1, and most of them were recovering/resolving or recovered/resolved without taking action. The serum exposure of LY-CovMab (C max , AUC 0–last , AUC 0–inf ) after intravenous infusion increased in an approximately proportional manner as the dose increased from 150 to 2400 mg. The elimination half-life ( t 1/2 ) value did not differ among different dose cohorts and was estimated to be around 28.5 days. Conclusions A single dose of LY-CovMab was shown to be safe and well tolerated in Chinese healthy adults. The pharmacokinetic (PK) profiles of LY-CovMab in healthy adults showed typical monoclonal antibody distribution and elimination characteristics. LY-CovMab demonstrated dose proportionality. Trial Registration ClinicalTrial.gov Identifier NCT04973735. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00572-x.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2

et al. 2021

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Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Strohl

et al. 2022

BioDrugs

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The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly’s bamlanivimab and etesevimab, Regeneron’s mixture of imdevimab and casirivimab, Vir’s sotrovimab, Celltrion’s regdanvimab, and Lilly’s bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00529-7.

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Animal models for studying coronavirus infections and developing antiviral agents and vaccines

Lin¹,

Lu²,

Hong³

et al. 2022

Antiviral Research

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Structure and function analysis of a potent human neutralizing antibody CA521FALA against SARS-CoV-2

Cited by 12 publications

References 37 publications

A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2

A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Animal models for studying coronavirus infections and developing antiviral agents and vaccines

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