Human neutralizing antibodies for SARS-CoV-2 prevention and immunotherapy

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 has been spreading worldwide since December 2019, resulting in the ongoing COVID-19 pandemic with 237 million infections and 4.8 million deaths by 11 October 2021. While there are great efforts of global vaccination, ending this pandemic has been challenged by issues of exceptionally high viral transmissibility, re-infection, vaccine-breakthrough infection, and immune escape variants of concern. Besides the record-breaking speed of vaccine research and development, antiviral drugs including SARS-CoV-2-specific human neutralizing antibodies (HuNAbs) have been actively explored for passive immunization. In support of HuNAb-based immunotherapy, passive immunization using convalescent patients' plasma has generated promising evidence on clinical benefits for both mild and severe COVID-19 patients. Since the source of convalescent plasma is limited, the discovery of broadly reactive HuNAbs may have significant impacts on the fight against the COVID-19 pandemic. In this review, therefore, we discuss the current technologies of gene cloning, modes of action, in vitro and in vivo potency and breadth, and clinical development for potent SARS-CoV-2-specific HuNAbs.

Keywords: SARS-CoV-2; immunotherapy; neutralizing antibody; passive immunization; vaccine.

Figure 1.

Categorized recognition sites of SARS-CoV-2 RBD-specific mAbs. (A) Conformational structure of SARS-CoV-2 trimer spike glycoprotein (PDB: 7BNM, 1 up RBD) with the ACE2 binding footprints (purple) on RBDs. (B) The crystal structure of RBD (white) is displayed in two orientations (PDB:7BNM, amino acid position: 320–540). The binding sites of different subclasses of mAbs are labelled in orange for mAb CB6 (RBS-A, PDB ID: 7C01), blue for mAb 2-4 (RBS-B, PDB ID: 6XEY), red for mAb P2B-2F6 (RBS-C, PDB ID: 7BWJ), green for mAb CR3022 (PDB ID: 6W41) cryptic site, and yellow for mAb S309 (PDB ID: 6WPS) proteoglycan site.