(P-CB-3) Anti-Spike and Nucleocapsid Antibody Dynamics Following SARS-CoV-2 Infection and Vaccination: Implications for Sourcing COVID-19 Convalescent Plasma

Background/Case Studies: COVID-19 Convalescent Plasma (CCP) remains a potential treatment option for immunosuppressed patients. However, regulatory criteria limit its collection to individuals with diagnosed, symptomatic infection and relatively low-level (>200 Binding Antibody Units (BAU)/ml) spike (S) reactivity. In this study we measured S and nucleocapsid (NC) binding and neutralizing antibody (bAb, nAb) levels and activity against different SARS-CoV-2 variants in serial repeat blood donors’ samples who were infected and/or vaccinated.

Study

Design/Methods: Longitudinal plasma samples (4-18) from allogeneic blood donors with and without symptomatic SARS-CoV2 infections, collected between 09/2020 and 06/2022, were categorized into 4 groups (30-60 donors/group [G]): infection followed by primary vaccination with optional booster (vax) (G1), vax followed by infection during the Delta (G2) or Omicron (G3) waves, and primary vax and booster without infection (G4). All the samples were tested with the Ortho VITROS Anti-SARS-CoV2 Total NC Ab and S IgG Quantitative tests. Multiple dilutions (neat, 1:20 or 1:400 as needed) were used to increase the dynamic range reported in BAU/mL. Key timepoints (7-9) were further characterized for S, receptor binding domain (RBD) and NC IgG bAb (MesoScale Diagnostic [MSD] arrays) and pseudovirus based nAb for the ancestral, Alpha, Beta, Gamma, Delta, and Omicron variants. Peak Ab values were imputed at 14 days after each event, and waning curves modeled from the longitudinal results.

Results/Findings: Ortho S IgG Ab peak after infection alone (G1, 2.3) were lower than after primary vax (G2-G4, 3.3-3.5) (Table 1), but these were similar following booster vax (G2-G4, 3.5-3.7). Slightly higher peaks were observed after the infections in G2 and G3. Overall among all groups, half-lives for S IgG ranged between 6-8 weeks after first event (infection or vax) and 15 weeks after second event, while NC total Ig was about 22 weeks and NC IgG 11. There were no differences in Ab levels or half-lives between symptomatic (all groups n=90) or asymptomatic donors (n=60). Levels of S IgG bAb (MSD) and nAb were similar across the different variants and mirrored the dynamics of Ortho S IgG levels, except for Ab to omicron which were lower than for other variants in all groups except the Omicron group, G3.

Conclusions: Plasma derived from blood donors vaccinated before or after infection contained high levels of S IgG Ab and showed high-titer neutralization to ancestral and variant S, irrespective of symptoms presentation. These findings have implications for criteria for qualification and potency of therapeutic passive Ab in CCP.

Importance of research: Current COVID-19 therapies are limited. COVID-19 convalescent plasma (CCP) with high-titers antibodies against SARS-CoV-2 variants may be efficacious for immunosuppressed patients at high-risk for poor infection outcomes. We demonstrated that plasma from blood donors who had experienced both vaccination and infection (symptomatic or asymptomatic) contain high levels of binding and neutralizing antibodies against multiple variants.