Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

Abstract

Background: Although 6 COVID-19 vaccines have been approved by the World Health Organisation as of 7th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines. Methods: Data from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralizing antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to outcome. Cubic spline smoothed log antibody levels, and baseline risk of exposure were the predictor variables with weights applied to account for selection bias in sample processing. Results: Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection. Conclusions: Correlates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.

Antibody Responses after a Third Dose of COVID-19 Vaccine in Kidney Transplant Recipients and Patients Treated for Chronic Lymphocytic Leukemia

“…Overall, this suggests that a third dose of COVID-19 vaccine in immunocompromised patients can increase antibody levels. Still, this increase might not be clinically relevant because few patients reached anti-spike IgG levels ≥ 30 BAU/mL, previously associated with 50% vaccine effectiveness [19]. These results are in line with other studies in kidney transplant recipients [10][11][12] and provide new data regarding patients with CLL.…”

“…This interpretation is limited by its lack of association with vaccine effectiveness and its lack of comparability with other assays, using different cut-offs. As such, results were also compared with a cut-off of 30 BAU/mL, recently associated with 50% vaccine effectiveness against symptomatic COVID-19 in immunocompetent patients [19]. All calculations were performed with Graph-Pad Prism 9.0 using Wilcoxon test (paired values), Mann-Whitney (unpaired values) and Fisher's exact test (binomial variables).…”

Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients

“…Phase 3 studies of authorised vaccines in the UK either excluded this particular patient group or did not report their renal disease subgroups. [5][6][7] Whereas anti-Spike (anti-S) antibody dynamics in in-centre haemodialysis patients have been described, 8 the levels of neutralising antibodies (nAbs) to the prevalent variants of concern (VOCs), which are emerging as the crucial serological correlate of protection, 9,10 have not been widely reported.…”

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

“…The present analysis assumes according to findings from previous reports that NA and anti-RBD are correlates of protection against SARS-CoV-2 [5,[21][22][23][24][25][26]31]. Although the mechanism of protection is complex including several aspects of humoral and cell-mediated immunity, the role of neutralizing antibodies seems profound.…”

“…A higher AZD1222 vaccine efficacy was demonstrated with higher levels of NA and anti-spike IgG in a vaccination trial [26]. Moreover, anti-RBD and anti-Spike binding assays were equivalent to NA in predicting vaccine efficacy for predicting symptomatic infection [26].…”