Higher Delta variant-specific neutralizing antibodies prevented infection in close contacts vaccinated with ancestral mRNA vaccines during the SARS-CoV-2 Delta wave

Abstract

Identification of the risk factors and the high-risk groups which are most vulnerable is critical in COVID-19 disease management at a population level. Evaluating the efficacy of vaccination against infections is necessary to determine booster vaccination strategies for better protection in high-risk groups. In this study, we recruited 158 mRNA-vaccinated individuals during the Delta wave of SARS-CoV-2 infections in Singapore and examined the antibody profiles of infected individuals. We found that, despite high exposure due to communal living conditions in proximity, 4% of individuals (6/158) had PCR-confirmed infections and 96% (152/158) remained uninfected. Time-course analysis of the antibody profile at the start and the end of quarantine period showed Delta-specific boosting of anti-spike antibody response in 57% of the uninfected individuals (86/152). In the remaining 43% of the uninfected individuals (66/152) with no Delta-specific antibody boost, we found a higher Delta-specific antibody response at the start of quarantine period, which correlated with higher Delta pseudovirus neutralizing capacity. Our findings indicate that a higher basal variant-specific antibody response in the mRNA-vaccinated individuals contributes to better protection against infections by the new emerging SARS-CoV-2 variants.

Figure 1

Antibody response against WT and Delta Spike. (A) PCR status of cohort (n = 158). (B) Plasma samples of all 158 individuals collected at the start of the quarantine (n = 158) were screened for binding by SFB assay. IgG binding against full-length WT and Delta Spike were compared for all 158 individuals (n = 158). Line indicates median IgG response. Pie chart indicates the proportion with positive antibody response (in pink) and proportion with negative response (in blue). Number in pie chart indicates the proportion with negative response. Positive antibody response is defined as response above mean + 3SD of 22 pre-COVID-19 unvaccinated healthy controls. (C) Paired analysis of all 158 individuals at the start and end of the quarantine were performed for IgG binding against full-length Delta Spike. Dotted line indicates positive antibody response, defined as response above mean + 3SD of 22 pre-COVID-19 unvaccinated healthy controls. Start, start of quarantine; End, end of quarantine. (D) The paired IgG responses at the start and the end of the quarantine of the 158 individuals in C were re-plotted, where the data points were stratified into three groups by PCR status and Delta Spike IgG seroconversion at the end of the quarantine period: (1) PCR-positive and Delta Spike IgG-seroconverted, PCR + Seroconv + (n = 6), (2) PCR-negative and Delta Spike IgG-seroconverted, PCR- Seroconv + (n = 86) and (3) PCR-negative without Delta Spike IgG-seroconversion, PCR- Seroconv- (n = 66). The IgG responses at start and end of the quarantine (from C) for the three groups were re-plotted. Start, start of quarantine; End, end of quarantine. Delta Spike IgG-seroconversion was defined as having an increase of Delta-Spike IgG binding of > 6.3% (mean + 3SD of 22 pre-COVID-19 unvaccinated healthy controls). To compare between two groups, Mann Whitney U-tests were used. For paired analysis, Wilcoxon tests were used. *p < 0.05; **p < 0.01; ****p < 0.0001; ns, non-significant.

Figure 2

Higher Delta-specific antibody in uninfected vaccinated individuals. Plasma samples were screened for (A) IgG binding against full-length Delta and (B) Delta pseudovirus neutralization at the start of the quarantine. The samples were classified into three groups: (1) PCR-positive and Delta Spike IgG-seroconverted (n = 6 for both assays), (2) PCR-negative and Delta Spike IgG-seroconverted (n = 86 and n = 30 for Delta-Spike binding and Delta pseudovirus neutralization respectively) and (3) PCR-negative without Delta Spike IgG-seroconversion (n = 66 and n = 29 for Delta-Spike binding and Delta pseudovirus neutralization respectively). To compare between groups at the start of the quarantine, points in A are re-plotted points from Fig. 1D (start of quarantine). Kruskal–Wallis and post hoc tests using Dunn’s multiple comparison tests were used to compare multiple groups. (C) Correlation analysis between Delta spike-specific IgG responses and Delta pseudovirus neutralization at the start of the quarantine. Non-parametric Spearman test was used for correlation analysis. *p < 0.05.