This panel of SARS-CoV-2-specific monoclonal antibodies has the potential to advance significant diagnostic, research, and therapeutic applications against COVID-19. Working with the U.S. Centers for Disease Control and Prevention (CDC), innovators at Georgia Tech developed and functionally characterized 158 nanomolar-affinity mouse monoclonal antibodies specific to SARS-CoV-2, using an accelerated immunization and hybridoma screening process. The innovation has the potential to produce an unmatched set of reagents for research and development.

Researchers focused on the receptor binding domain (RBD) with approximately 300 amino acids within the S1 subunit of the spike protein because of its key interaction with the human angiotensin-converting-enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. The research team identified three groups of neutralizing antibodies recognizing distinct epitopes on the RBD motif with high affinity, as inferred from sequence and competitive binding experiments. Additionally, differing functions—including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue—were correlated with variable gene usage and sequence.

The researchers further determined that the antibody response to the SARS-CoV-2 RBD can be functionally diverse, which can have significant utility in a variety of applications. Data to support SARS-CoV-2-specific binding include enzyme-linked immunosorbent assay (ELISA) and label-free binding measurements using recombinant proteins, immunofluorescence in culture, immunofluorescence staining of tissue from infected patients, and virus neutralization assays.