Most therapeutic monoclonal antibodies target the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (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 monoclonal antibodies. Universal monoclonal antibodies for different variants are necessary. We identified monoclonal antibodies that recognized the S2 region of the spike protein, which is identical in different variants. The monoclonal antibodies 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 monoclonal antibody (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 monoclonal antibody, which is not mutated in any variant of concern (VOC). These data suggest that a monoclonal antibody recognizing the S2 region of the spike protein will be a potential universal therapeutic monoclonal antibody for COVID-19.
Date:
2022-04-22
Relation:
JCI Insight. 2022 Apr 22;7(8):Article number e157597.
