Microfluidic Diffusional Sizing (MDS) Measurements of Secretory Neutralizing Antibody Affinity Against SARS-CoV-2

Ann Biomed Eng. 2024 Jun;52(6):1653-1664. doi: 10.1007/s10439-024-03478-0. Epub 2024 Mar 8.

Abstract

SARS-CoV-2 has rampantly spread around the globe and continues to cause unprecedented loss through ongoing waves of (re)infection. Increasing our understanding of the protection against infection with SARS-CoV-2 is critical to ending the pandemic. Serological assays have been widely used to assess immune responses, but secretory antibodies, the essential first line of defense, have been studied to only a limited extent. Of particular interest and importance are neutralizing antibodies, which block the binding of the spike protein of SARS-CoV-2 to the human receptor angiotensin-converting enzyme-2 (ACE2) and thus are essential for immune defense. Here, we employed Microfluidic Diffusional Sizing (MDS), an immobilization-free technology, to characterize neutralizing antibody affinity to SARS-CoV-2 spike receptor-binding domain (RBD) and spike trimer in saliva. Affinity measurement was obtained through a contrived sample and buffer using recombinant SARS-CoV-2 RBD and monoclonal antibody. Limited saliva samples demonstrated that MDS applies to saliva neutralizing antibody measurement. The ability to disrupt a complex of ACE2-Fc and spike trimer is shown. Using a quantitative assay on the patient sample, we determined the affinity and binding site concentration of the neutralizing antibodies.

Keywords: Microfluidic diffusional sizing; Neutralizing antibody; SARS-CoV-2; Saliva.

MeSH terms

  • Angiotensin-Converting Enzyme 2* / chemistry
  • Angiotensin-Converting Enzyme 2* / immunology
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / immunology
  • Antibody Affinity
  • COVID-19* / immunology
  • Humans
  • SARS-CoV-2* / immunology
  • Saliva / immunology
  • Spike Glycoprotein, Coronavirus* / chemistry
  • Spike Glycoprotein, Coronavirus* / immunology

Substances

  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus
  • Angiotensin-Converting Enzyme 2
  • spike protein, SARS-CoV-2
  • Antibodies, Viral
  • ACE2 protein, human
  • Antibodies, Monoclonal