Dataset Information

Rapid isolation of pan-neutralizing antibodies against Omicron variants from convalescent individuals infected with SARS-CoV-2.

ABSTRACT:

Introduction

The emergence of SARS-CoV-2 Omicron subvariants has presented a significant challenge to global health, as these variants show resistance to most antibodies developed early in the pandemic. Therapeutic antibodies with potent efficacy to the Omicron variants are urgently demanded.

Methods

Utilizing the rapid antibody discovery platform, Berkeley Lights Beacon, we isolated two monoclonal neutralizing antibodies, 2173-A6 and 3462-A4. These antibodies were isolated from individuals who recently recovered from Omicron infections.

Results

Both antibodies, 2173-A6 and 3462-A4, demonstrated high affinity for the RBD and effectively neutralized pseudoviruses from various Omicron lineages, including BA.4/5, XBB.1.16, XBB.1.5, and EG.5.1. This neutralization was achieved through binding to identical or overlapping epitopes.

Discussion

The use of the Beacon platform enabled the rapid isolation and identification of effective neutralizing antibodies within less than 10 days. This process significantly accelerates the development of novel therapeutic antibodies, potentially reducing the time required to respond to unknown infectious diseases in the future.

SUBMITTER: Yu P

PROVIDER: S-EPMC10950932 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Rapid isolation of pan-neutralizing antibodies against Omicron variants from convalescent individuals infected with SARS-CoV-2.

Yu Peng P Ran Jingping J Yang Ruiqi R Zhu Hang H Lu Song S Wu Yuzhang Y Zhao Tingting T Xiong Tianchen T

Frontiers in immunology 20240306

<h4>Introduction</h4>The emergence of SARS-CoV-2 Omicron subvariants has presented a significant challenge to global health, as these variants show resistance to most antibodies developed early in the pandemic. Therapeutic antibodies with potent efficacy to the Omicron variants are urgently demanded.<h4>Methods</h4>Utilizing the rapid antibody discovery platform, Berkeley Lights Beacon, we isolated two monoclonal neutralizing antibodies, 2173-A6 and 3462-A4. These antibodies were isolated from i ...[more]

PMID: 38510237

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Project description:BackgroundThe ongoing emergence of evolving SARS-CoV-2 variants poses great threaten to the efficacy of authorized monoclonal antibody-based passive immunization or treatments. Developing potent broadly neutralizing antibodies (bNabs) against SARS-CoV-2 and elucidating their potential evolutionary pathways are essential for battling the coronavirus disease 2019 (COVID-19) pandemic.MethodsBroadly neutralizing antibodies were isolated using single cell sorting from three COVID-19 convalescents infected with prototype SARS-CoV-2 strain. Their neutralizing activity against diverse SARS-CoV-2 strains were tested in vitro and in vivo, respectively. The structures of antibody-antigen complexes were resolved using crystallization or Cryo-EM method. Antibodyomics analyses were performed using the non-bias deep sequencing results of BCR repertoires.ResultsWe obtained a series of RBD-specific monoclonal antibodies with highly neutralizing potency against a variety of pseudotyped and live SARS-CoV-2 variants, including five global VOCs and some Omicron subtypes such as BA.1, BA.2, BA.4/5, BF.7, and XBB. 2YYQH9 and LQLD6HL antibody cocktail also displayed good therapeutic and prophylactic efficacy in an XBB.1.16 infected hamster animal model. Cryo-EM and crystal structural analyses revealed that broadly neutralizing antibodies directly blocked the binding of ACE2 by almost covering the entire receptor binding motif (RBM) and largely avoided mutated RBD residues in the VOCs, demonstrating their broad and potent neutralizing activity. In addition, antibodyomics assays indicate that the germline frequencies of RBD-specific antibodies increase after an inactivated vaccine immunization. Moreover, the CDR3 frequencies of Vκ/λ presenting high amino acid identity with the broadly neutralizing antibodies were higher than those of VH.ConclusionsThese data suggest that current identified broadly neutralizing antibodies could serve as promising drug candidates for COVID-19 and can be used for reverse vaccine design against future pandemics.

Dataset Information

Rapid isolation of pan-neutralizing antibodies against Omicron variants from convalescent individuals infected with SARS-CoV-2.

Introduction

Methods

Results

Discussion

Publications

Rapid isolation of pan-neutralizing antibodies against Omicron variants from convalescent individuals infected with SARS-CoV-2.

Similar Datasets

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