SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants

Tea, F.; Ospina Stella, A.; Aggarwal, A.; Darley, D. R.; Pilli, D.; Vitale, D.; Merheb, V.; Lee, F. X. Z.; Cunningham, P.; Walker, G. J.; Brown, D. A.; Rawlinson, W. D.; Isaacs, S. R.; Mathivanan, V.; Hoffman, M.; Poehlmann, S.; Dwyer, D. E.; Rockett, R.; Sintchenko, V.; Hoad, V. C.; Irving, D. O.; Dore, G. J.; Gosbell, I. B.; Kelleher, A. D.; Matthews, G. V.; Brilot, F.; Turville, S. G.

The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of high responders maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.