Broadly neutralizing human mAbs targeting the SARS‑CoV‑2 spike protein

Problem

Monoclonal antibodies (mAbs) that target the SARS-CoV-2 spike protein have been shown to have clinical benefits in the treatment of SARS-CoV-2 infection. The activity of anti-SARS-CoV-2 mAbs against specific variants and subvariants of this virus can vary dramatically. There is a clinical need for continued identification of anti-SARS-CoV-2 mAbs for therapeutic and diagnostic applications.

Solution

Dr. Ippolito, Dr. Lavinder, and their research team have discovered and verified mAbs that are reactive with the S1 and S2 subunits of the spike protein of SARS-CoV-2. The team used an approach combining high-throughput sequencing of B‑cell receptors and mass-spectrometry to identify mAbs from human blood that bind to the Spike protein of SARS-CoV‑2, the causative agent of COVID-19. These mAbs have the potential to serve as a powerful diagnostic, prophylactic or therapeutic for monitoring, containing or treating SARS-CoV-2.

The lead molecule in this portfolio, SC27, is pan-sarbecovirus mAb that targets the Spike Receptor Binding Domain which (1) has the highest intrinsic binding affinity yet reported for any mAb described or licensed since 2020 (< 5 pM), (2) broadly neutralizes live viruses across clade 1a and 1b including zoonotic bat and pangolin viruses as well as all historical omicron variants of concern, and (3) protects mice when challenged with a lethal dose of mouse-adapted SARS-CoV-2.

About the inventors

Dr. Ippolito is a Research Associate Professor in Molecular Biosciences and an Associate Professor of Oncology in the Department of Oncology at UT Austin and Dell Medical School. Dr. Ippolito has participated in authoring dozens of journal publications in his area of expertise since 2006. The focus of his work has broad applicability in the medical sector and targets normal and malignant B-cell development and the ontogeny of antibody repertoires in health and disease.

Dr. Lavinder is a Research Assistant Professor in Chemical Engineering at UT Austin. Dr. Lavinder has authored several papers in the field of structural biology and antibody discovery. The focus of his most recent work has applications in SARS-CoV-2 therapy and detection.

Patent Information: