TOP-Plus is a Versatile Biosensor Platform for Monitoring SARS-CoV-2 Antibody Durability

Racine-Brzostek, Sabrina E; Karbaschi, Mohsen; Gaebler, Christian; Klasse, P J; Yee, Jim; Caskey, Marina; Yang, He S; Hao, Ying; Sukhu, Ashley; Rand, Sophie; Chadburn, Amy; Shi, Yuanyuan; Zuk, Robert; Nussenzweig, Michel C; Cushing, Melissa M; Zhao, Zhen

BACKGROUND: Low initial SARS-CoV-2 antibody titers dropping to undetectable levels within months after infection have raised concerns over long term immunity. Both the antibody levels and avidity of the antibody-antigen interaction should be examined to understand the quality of the antibody response. METHODS: A testing-on-a-probe “plus” panel (TOP-Plus) was developed, which included a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months post-infection in paired samples from 80 COVID-19 patients. Sera from SARS-CoV-2 vaccinated individuals were also evaluated for antibody avidity. RESULTS: The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r=0.88). The imprecision of the TOP avidity assay was less than 10%. Although TAb and neutralization activity (by SNAb) decreased between 1.3 and 6.2 months post-infection, the antibody avidity increased significantly (P < 0.0001). Antibody avidity in 10 SARS-CoV-2 vaccinated individuals (median 28 days post-vaccination) was comparable to the measured antibody avidity in infected individuals (median 26 days post-infection). CONCLUSION: This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only SARS-CoV-2-infected patients, but also the status of individuals’ COVID-19 vaccination response.