Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.
Keywords: B.1.1.7; B.1.351; D614G; JMB2002; SARS-CoV-2; broad-spectrum; neutralizing antibody; phage-to-yeast; rhesus macaque disease model.
【저자키워드】 neutralizing antibody, SARS-CoV-2, B.1.351, B.1.1.7, D614G, JMB2002, broad-spectrum, phage-to-yeast, rhesus macaque disease model., 【초록키워드】 COVID-19, coronavirus disease, convalescent plasma, neutralizing antibody, Vaccine, coronavirus, clinical trial, Neutralizing antibodies, antibody, B.1.351, neutralization, COVID-19 pandemic, Phase 1 clinical trial, SARS-CoV-2 variant, Infection, Intervention, Transmission, severe acute respiratory syndrome coronavirus-2, in vitro, Prophylactic, severe acute respiratory syndrome Coronavirus, virus, angiotensin-converting enzyme 2, hACE2, Receptor binding domain, coronavirus disease-2019, Severe acute respiratory syndrome, Protein, SARS-CoV-2 variants, B.1.1.7, RBD, sera, therapeutic, D614G, Neutralizing, respiratory, disease, platform, yeast, binding, rhesus macaque, Angiotensin-converting enzyme, Coronavirus-2, angiotensin, lead, Phase 1, host cell, acute respiratory syndrome, acute respiratory syndrome coronavirus, therapeutic efficacy, sequence, host cell receptor, rhesus, blocking activity, phage, Complete, demonstrated, interact, the RBD, cause, the SARS-CoV-2, 【제목키워드】 Efficacy, antibody, blocking activity,