Method for the Rapid Detection of SARS-CoV-2-Neutralizing Antibodies Using a Nanogel-Based Surface Plasmon Resonance Biosensor

The efficacy of coronavirus disease 2019 (COVID19) vaccination is closely related to the serum levels of SARS-CoV2-neutralizing antibodies (NAb) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Therefore, the rapid and quantitative measurement of SARS-CoV-2 NAb in the sera of vaccinated individuals is essential to develop an effective vaccine and further achieve population immunity, that is, herd immunity. The plaque reduction neutralization test, the gold standard for NAb effectiveness in serological tests, is accurate but requires biosafety level 3 facilities because of the use of the virus, which hampers its application in common laboratories and clinical practice. Here, we developed a bioresponsive nanogel-based surface plasmon resonance (nSPR) platform that detects SARS-CoV-2 NAb in clinical samples without complicated pretreatment. We found that multivalent protein binding (MPB) between the nanogelconjugated RBD protein and SARS-CoV-2 NAb yields significantly enhanced SPR signals compared to the nonspecific interference from serum proteins in the nSPR assay. The excellence of our nanogel-based SARS-CoV-2 NAb test is due to its selectivity for NAb, with resistance to all other proteins, allowing the rapid detection and quantification of NAbs in each individual. Importantly, this nSPR assay provides a NAb detection platform for easier and safer COVID-19 vaccination strategies.

Automated summary

The efficacy of COVID-19 vaccination relies on the levels of SARS-CoV-2-neutralizing antibodies (NAbs) in the serum. A bioresponsive nanogel-based surface plasmon resonance (nSPR) platform has been developed to detect SARS-CoV-2 NAbs in clinical samples without complicated pretreatment. The nanogel-based NAb test shows excellent selectivity, rapid detection, and quantification of NAbs in each individual, providing a safer and easier NAb detection platform for COVID-19 vaccination strategies.