Dataset Information

Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant.

ABSTRACT:

Introduction

Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective.

Methods

We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model.

Results

Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant.

Conclusions

Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.

SUBMITTER: Wen K

PROVIDER: S-EPMC10461085 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant.

Wen Kun K Cai Jian-Piao JP Fan Xiaodi X Zhang Xiaojuan X Luo Cuiting C Tang Kai-Ming KM Shuai Huiping H Chen Lin-Lei LL Zhang Ricky Ruiqi RR Situ Jianwen J Tsoi Hoi-Wah HW Wang Kun K Chan Jasper Fuk-Woo JF Yuan Shuofeng S Yuen Kwok-Yung KY Zhou Hongwei H To Kelvin Kai-Wang KK

Frontiers in cellular and infection microbiology 20230814

<h4>Introduction</h4>Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective.<h4>Methods</h4>We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutra ...[more]

PMID: 37645378

Similar Datasets

Project description:The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by the emergence of variants of concern (VOCs), which have acquired mutations to escape neutralizing antibodies (nAbs). These mutations are not evenly distributed on the RBD surface but cluster on several distinct surfaces, suggesting an influence of the targeted epitope on the capacity to neutralize a broad range of VOCs. Here, we identified a potent nAb from convalescent patients targeting the receptor-binding domain of a broad range of SARS-CoV-2 VOCs. Except for the Lambda and BA.2.86 variants, this nAb efficiently inhibited the entry of most tested VOCs, including Omicron subvariants BA.1, BA.2, XBB.1.5, and EG.5.1 and to a limited extent also BA.4/5, BA.4.6, and BQ.1.1. It bound recombinant S protein with picomolar affinity, reduced the viral load in the lung of infected hamsters, and prevented the severe lung pathology typical for SARS-CoV-2 infections. An X-ray structure of the nAb-RBD complex revealed an epitope that does not fall into any of the conventional classes and provided insights into its broad neutralization properties. Our findings highlight a conserved epitope within the SARS-CoV-2 RBD that should be preferably targeted by therapeutic antibodies and inform rational vaccine development.IMPORTANCETherapeutic antibodies are effective in preventing severe disease from SARS-CoV-2 infection and constitute an important option in pandemic preparedness, but mutations within the S protein of virus variants (e.g., a mutation of L452) confer resistance to many of such antibodies. Here, we identify a human antibody targeting the S protein receptor-binding domain (RBD) with an elevated escape barrier and characterize its interaction with the RBD functionally and structurally at the atomic level. A direct comparison with reported antibodies targeting the same epitope illustrates important differences in the interface, providing insights into the breadth of antibody binding. These findings highlight the relevance of an extended neutralization profiling in combination with biochemical and structural characterization of the antibody-RBD interaction for the selection of future therapeutic antibodies, which may accelerate the control of potential future pandemics.

Dataset Information

Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant.

Introduction

Methods

Results

Conclusions

Publications

Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets