Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy

Abstract

Introduction: The duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans.

Methods: We recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections.

Results: Within two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p < 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination.

Discussion: Our results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.

Keywords: AstraZeneca vaccine; IgG; IgM; Ugandan population; and IgA antibody responses; hybrid immunity; nucleoprotein-directed antibodies; spike-directed antibodies.

Figure 1

Graphical Illustration of the Cohort Time Points and Specimen Collection. Figure 1 summarises the vaccination and specimen collection time points, beginning shortly before priming and continuing for up to one year after the initial vaccination.

Figure 2

Individual profile plots of spike-directed IgG, IgM and IgA antibody optical densities and concentrations after vaccination. Figure 2 shows the individual profile plots of spike-directed IgG (A), IgM (B), and IgA (C) antibody OD values (nm) and concentrations (ng/ml) over 12 months since the initial vaccination of individuals previously infected with mild or asymptomatic COVID-19. The dashed horizontal lines represent the cut-off points for antibody OD value seropositivity. The cut-offs for spike-directed IgG, IgM, and IgA seropositivity were 0.432, 0.459 and 0.226, respectively.

Figure 3

Percentage of seropositive participants following vaccination. Figure 3 illustrates the proportion (%) of participants with spike-directed IgG (A), IgM (B), IgA (C), and anti-nucleoprotein IgM (D) ad IgG (E) antibodies at various follow-up time points after vaccination (x-axis). (F) is a bar graph depicting the proportion of breakthrough subjects, defined as those who experienced an 11-fold increase in the concentration of nucleoprotein-directed IgG antibodies at each time point.

Figure 4

Box plots comparing vaccine-induced median spike-directed IgG, IgM and IgA antibody levels over time Figure 4 uses the Wilcoxon signed rank test to compare median OD values at 450 nm and concentrations (ng/ml) of the spike-directed IgG, IgM, and IgA antibody levels across time points. OD at 450nm and concentrations are shown for IgG (A), IgM (B), and IgA (C). P-values for differences between OD values or concentrations across adjacent time points are indicated. Horizontal dashed lines indicate cut-offs for the respective antibody isotypes. P values of 0.05 or less are considered statistically significant. The cut-offs for spike-directed IgG, IgM and IgA seropositivity were 0.432, 0.459 and 0.226, respectively.

Figure 5

shows the median trajectories of IgG, IgM, and IgA at after vaccination ( Figure 5 ) shows the median spike - (A) and nucleoprotein-directed (B) IgG, IgM, and IgA antibody OD values (m) and concentrations (ng/ml) over time, medians at a specific time point are plotted. The cut-offs for spike-directed IgG, IgM and IgA seropositivity were 0.432, 0.459 and 0.226, respectively. The cut-offs for nucleoprotein-directed IgG, IgM and IgA seropositivity were 0.454, 0.229 and 0.225, respectively.

Figure 6

Median fold change in in spike-directed antibody levels over time. Figure 6 summarises the fold change in spike-directed IgG, IgM and IgA antibody OD values (A) and concentrations (B) across the different specimen collection time points. The heat map shows the extent of change (increase or decrease) in vaccine-induced antibody response over time. The change between time points is shown with each cell indicating an increase or decrease between any two timepoints at the x and y axis. Fold change between 0 to 1 indicate a decrease (orange), Fold change of 1 indicates no change while fold change greater than 1 indicate an increase (purple).