The subdued post-boost spike-directed secondary IgG antibody response in Ugandan recipients of the Pfizer-BioNTech BNT162b2 vaccine has implications for local vaccination policies

Abstract

Introduction: This study aimed to delineate longitudinal antibody responses to the Pfizer-BioNTech BNT162b2 COVID-19 vaccine within the Ugandan subset of the Sub-Saharan African (SSA) demographic, filling a significant gap in global datasets.

Methods: We enrolled 48 participants and collected 320 specimens over 12 months after the primary vaccination dose. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibody concentrations (ng/ml) and optical densities (ODs). Statistical analyses included box plots, diverging bar graphs, and the Wilcoxon test with Bonferroni correction.

Results: We noted a robust S-IgG response within 14 days of the primary vaccine dose, which was consistent with global data. There was no significant surge in S-IgG levels after the booster dose, contrasting trends in other global populations. The S-IgM response was transient and predominantly below established thresholds for this population, which reflects its typical early emergence and rapid decline. S-IgA levels rose after the initial dose then decreased after six months, aligning with the temporal patterns of mucosal immunity. Eleven breakthrough infections were noted, and all were asymptomatic, regardless of the participants' initial S-IgG serostatus, which suggests a protective effect from vaccination.

Discussion: The Pfizer-BioNTech BNT162b2 COVID-19 vaccine elicited strong S-IgG responses in the SSA demographic. The antibody dynamics distinctly differed from global data highlighting the significance of region-specific research and the necessity for customised vaccination strategies.

Keywords: IgG IgM and IgA antibodies; Pfizer BioNTech BNT162b2 COVID-19 vaccine; Sub-Saharan African populations; Ugandan population; booster dose; breakthrough infections; longitudinal antibody responses; seropositivity classification.

Figure 1

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine Administration and Sample Collection schedule. This figure illustrates vaccination and sample collection from 48 participants, detailing the number of samples obtained at each time point and the the number of subjects that were baseline S-IgG+ and baseline S-IgG-.

Figure 2

Rates of Spike Protein-Directed Seroconversion Following Pfizer-BioNTech COVID-19 (BNT162b2) Vaccination. This figure shows the percentage of participants who seroconverted at each time point. Using cutoffs of 0.432 for S-IgG, 0.459 for S-IgM, and 0.226 for S-IgA, the 320 samples were categorized as either positive or negative for IgG (A), IgM (B) and IgA (C) antibodies. The bar graphs represent the proportion of participants with positive or negative status at each interval.

Figure 3

Comparative Analysis of Spike-Directed Antibody Responses: Boxplot Representation Across Different Time Points. This figure shows the distribution of antibody responses over time using boxplots, highlighting the median (lines), mean (black circles), and quartiles for IgG (A, B), IgM (C, D) and IgA (E, F). Significant differences between adjacent time points were assessed using an unpaired Wilcoxon test with a Bonferroni correction for multiple testing. Notation ns denotes p-values > 0.05 and was considered insignificant. *p ≤ 0.05, **p < 0.01, and ****p < 0.0001, indicating increasing levels of statistical significance.

Figure 4

Individual Antibody Response Profiles Categorized by Baseline Spike Protein IgG Seropositivity. This figure shows the antibody responses against the Spike protein, including IgG (A, B), IgM (C, D), and IgA (E, F). Participants were colour-coded based on S-IgG seropositivity at baseline: positive in pink (S-IgG levels ≥ S-IgG cutoff) and negative in blue. Thick lines indicate group median values, while thin lines depict individual profiles.

Figure 5

Variations in anti-Spike Antibody Levels and Incidence of Breakthrough Infections Following Pfizer-BioNTech COVID-19 (BNT162b2) Vaccination. Median antibody level changes over time, presented as optical density (OD) levels (A) and concentrations (B), using red for increases and green for decreases, alongside the percentage and number of breakthrough cases at each time point (C).

Figure 6

Longitudinal Analysis of BNT162b2-Induced Spike-Specific Antibody Responses in Baseline S-IgG Seropositive Individuals Over 12 months. Boxplots visually summarizing for 23 individuals that were seropositive for spike-directed IgG antibodies at baseline displaying temporal dynamics of spike-directed IgG (A, B), IgM (C, D), and IgA (E, F) antibody responses over the 12 months of follow up. in baseline S-IgG+ participants, with median lines, mean as black circles, and quartiles at box edges. Differences between time points were assessed using an unpaired Wilcoxon test with Bonferroni correction, denoted as ns (p > 0.05) and *(p ≤ 0.05).

Figure 7

Comprehensive Analysis of the Pfizer-BioNTech BNT162b2 Vaccine-induced Spike-Directed Antibody Responses in S-IgG- Participants Over Time. Illustrates the dynamics of the Pfizer-BioNTech BNT162b2 vaccine-induced Spike-directed antibody responses (IgG, IgM, IgA) in 20 participants initially lacking anti-spike IgG (S-IgG) at baseline (Day 0). Panels (A–F) show the distribution of antibody optical density (OD) levels and concentrations in ng/ml across time points for IgG (A, B), IgM (C, D), and IgA (E, F). Statistical analysis involved the Wilcoxon test for unpaired pairwise comparisons, with Bonferroni correction for multiple testing, to address missing data points. Boxplots display median (line), mean (black circle), and quartile values (box edges). Significance levels are indicated as: ns (p > 0.05), *(p ≤ 0.05), **(p < 0.01), ***(p < 0.001), ****(p < 0.0001).