Convalescent plasma donors show enhanced cross-reactive neutralising antibody response to antigenic variants of SARS-CoV-2 following immunisation.

BACKGROUND: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralising antibodies (nAbs) to SARS-CoV-2. To investigate effects of antigenic variation on neutralisation potency of CP, we compared nAb titres against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunisation. METHODS AND MATERIALS: Samples were assayed from previously SARS-CoV-2 infected donors before (n=17) and after one (n=43) or two (n=71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titres against Wuhan/wild type (WT), Alpha, Beta and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titres to Omicron used a focus reduction neutralisation test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). RESULTS: Unvaccinated donors showed a geometric mean titre (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralise Beta, Delta and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/ml was highly predictive of donations with nAb titres of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specifciity) DISCUSSION: Vaccination of previously infected CP donors induced high levels of broadly neutralising antibodies against circulating antigenic variants of SARS-CoV-2. High titre donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale pre- selection of high-titre convalescent plasma.