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

Front Cell Infect Microbiol. 2023 Aug 14:13:1213806. doi: 10.3389/fcimb.2023.1213806. eCollection 2023.

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.

Keywords: SARS-CoV-2; monoclonal antibody; prophylaxis; therapeutics; variants of concern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing
  • COVID-19*
  • Cricetinae
  • Humans
  • Mice
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work was funded by the Health@InnoHK, Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region; the National Program on Key Research Project of China (grant no. 2020YFA0707500 and 2020YFA0707504); and the donations of the Shaw Foundation Hong Kong, Richard Yu and Carol Yu, May Tam Mak Mei Yin, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, and Marina Man-Wai Lee. The funding sources had no role in study design, data collection, analysis, interpretation or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.