Rapid and lasting generation of B-cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 disease and convalescence

G. E. Hartley, E. Edwards, P. Aui, N. Varese, S. Stojanovic, J. McMahon, A. Peleg, I. Boo, H. Drummer, P. Hogarth, R. O’Hehir, M. V. van Zelm

medRxiv, 2020

Background: Lasting immunity to SARS-CoV-2 following infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Objective: To determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. Methods: Recombinant spike receptor binding domain (RBD) and nucleocapsid protein (NCP) were produced for ELISA-based serology, and biotinylated for fluorescent tetramer generation to identify SARS-CoV-2-specific Bmem cells by flow cytometry with a panel of 13 mAbs. 36 blood samples were obtained from 25 COVID-19 patients (11 paired) between 4-242 days post-symptom onset for detection of neutralizing antibodies, IgG serology and flow cytometry. Results: The recombinant RBD and NCP were specifically recognized by serum IgG in all patients and reactivity declined >20 days post-symptom onset. All patients had detectable RBD- and NCP-specific Bmem cells at 8.23-267.6 cells/ml of blood (0.004-0.13% of B cells) regardless of sampling time. RBD- and NCP-specific Bmem cells predominantly expressed IgM or IgG1, with the latter formed slightly later than the former. RBD-specific IgG+ Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers. Conclusion: RBD- and NCP-specific Bmem cells persisted for 8 months, indicating that the decline in serum antibodies after 1 month does not indicate waning of immunity but a contraction of the immune response. Flowcytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term functional immunity following infection or vaccination for COVID-19.

Cited by 4 publications.

Field of study: Medicine

10.1101/2020.11.17.20233544