Abstract
Administration of convalescent plasma or neutralizing monoclonal antibodies (mAbs) is a potent therapeutic option for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged in many countries. To evaluate the efficacy of neutralizing antibodies induced in convalescent patients against emerging variants, we isolate anti-spike mAbs from two convalescent COVID-19 patients infected with prototypic SARS-CoV-2 by single-cell sorting of immunoglobulin-G-positive (IgG+) memory B cells. Anti-spike antibody induction is robust in these patients, and five mAbs have potent neutralizing activities. The efficacy of most neutralizing mAbs and convalescent plasma samples is maintained against B.1.1.7 and mink cluster 5 variants but is significantly decreased against variants B.1.351 from South Africa and P.1 from Brazil. However, mAbs with a high affinity for the receptor-binding domain remain effective against these neutralization-resistant variants. Rapid spread of these variants significantly impacts antibody-based therapies and vaccine strategies against SARS-CoV-2.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which emerged in late 2019 and became a pandemic (Wu et al, 2020a; Zhou et al, 2020; Zhu et al, 2020)
Hundreds of monoclonal antibodies against SARS-CoV-2 have been isolated from convalescent COVID-19 patients (Barnes et al, 2020; Brouwer et al, 2020; Cao et al, 2020; Kim et al, 2021; Kreye et al, 2020; Liu et al, 2020a), and potent neutralizing mAbs, which mostly target the receptor-binding domain (RBD) of the SARSCoV-2 spike (S) protein, have been developed for clinical use (Schafer et al, 2021; Weinreich et al, 2021)
Isolation of neutralizing mAbs from two convalescent patients To identify potent neutralizing mAbs against SARS-CoV-2, we selected two patients, A and B, who had recovered from severe COVID-19 (Table S1)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which emerged in late 2019 and became a pandemic (Wu et al, 2020a; Zhou et al, 2020; Zhu et al, 2020). Hundreds of monoclonal antibodies (mAbs) against SARS-CoV-2 have been isolated from convalescent COVID-19 patients (Barnes et al, 2020; Brouwer et al, 2020; Cao et al, 2020; Kim et al, 2021; Kreye et al, 2020; Liu et al, 2020a), and potent neutralizing mAbs, which mostly target the receptor-binding domain (RBD) of the SARSCoV-2 spike (S) protein, have been developed for clinical use (Schafer et al, 2021; Weinreich et al, 2021). It is important to clarify whether neutralizing antibodies from convalescent patients infected with the prototypic virus are effective against emerging SARS-CoV-2 variants for therapy using plasma or antibodies from convalescent patients. We examined the sensitivity of neutralizing mAbs and plasma from convalescent patients to emerging SARS-CoV-2 variants
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