Rapid Characterization and Selection of SARS-CoV-2 Vaccine Candidates by Bio-Layer Interferometry (BLI) Technology
Wei-Hung Chen, PhD, Research Scientist, Walter Reed Army Institute of Research, The Emerging infectious disease branch
SARS-CoV-2 is a zoonotic coronavirus that has caused a global pandemic with more than 10 million confirmed infections across more than 200 countries. The severity of the COVID-19 outbreak highlights the need to develop therapeutic interventions including vaccines, small molecule inhibitors, and immunotherapeutics. Using BLI, we developed a set of assays to identify antibodies with SARS-CoV-2 reactivity, and to enable rapid characterization of SARS-CoV-2 vaccine candidates. Initially, we tested a set of SARS-CoV monoclonal antibodies obtained from BEI resources to assess cross-reactivity to SARS-CoV-2 Spike glycoprotein.
These antibodies target a conserved epitope present on SARS-CoV and related beta-coronaviruses centered on the receptor-binding domain Proline 384. Using this set of re-purposed antibodies and an additional set of potent neutralizing antibodies, we carried out antigenic screening of more than 100 SARS-CoV-2 nanoparticle vaccine candidates. A subset of these immunogens were assessed in mouse immunogenicity studies. Using BLI, we assessed the vaccine-elicited serum response against the SARS-CoV-2 receptor binding domain (RBD) to enable down-selection of vaccine candidates. In addition, using recombinant ACE2 receptor protein, we developed an ACE2 inhibition assay to assess the vaccine-elicited serum ACE2 inhibitory activity. BLI also allows same-day investigation of newly produced protein candidate immunogens, and rapid analysis of animal sera immune responses.