Monoclonal antibody targeting the conserved region of the SARS-CoV-2 spike protein to overcome viral variants.

Wan-Ling Wu,Ching-Len Liao,Hung-Chun Liao,Shih-Jen Liu,Hsin-Wei Chen,Chia-Yi Yu,Yu-Ling Huang,Chen-Yi Chiang,Szu-Chia Lai

doi:10.1172/jci.insight.157597

Abstract

Most therapeutic mAbs target the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Unfortunately, the RBD is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs. Universal mAbs for different variants are necessary. We identified mAbs that recognized the S2 region of the spike protein, which is identical in different variants. The mAbs could neutralize SARS-CoV-2 infection and protect animals from SARS-CoV-2 challenge. After cloning the variable region of the light chain and heavy chain, the variable region sequences were humanized to select a high-affinity humanized mAb, hMab5.17. hMab5.17 protected animals from SARS-CoV-2 challenge and neutralized SARS-CoV-2 variant infection. We further identified the linear epitope of the mAb, which is not mutated in any variant of concern. These data suggest that a mAb recognizing the S2 region of the spike protein will be a potential universal therapeutic mAb for COVID-19.

Highlights

The COVID-19 outbreak is an emerging global health threat, and the virus continues to spread worldwide
The receptor-binding domain (RBD) is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs
These observations clearly indicated that the 2 mAbs have the potential to neutralize SARS-CoV-2 through specific recognition of CB-119 located in the HR2 region of the spike protein

Summary

Introduction

The COVID-19 outbreak is an emerging global health threat, and the virus continues to spread worldwide. SARS-CoV-2, a betacoronavirus, is the major cause of COVID-19 [1, 2]. The total number of COVID-19 cases exceeded 250 million infections and 5 million deaths as of November 10, 2021 [3]. Even though COVID-19 vaccines are available to prevent illness for most of the world, the epidemic is still increasing sharply in many parts of the world, with little sign of slowing. The rapid development of safe and effective new drugs for COVID-19 treatment is of particular concern. The efficacy of passive immunization with convalescent plasma to cure COVID-19 has been proven, resulting in clinical improvement [4, 5]; the development of neutralizing mAbs is one of the most promising approaches for clinical use and can complement the use of vaccines to block infection in patients with SARS-CoV-2 [6]

Methods

Results

Conclusion