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

IntroductionThis 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.MethodsWe 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.ResultsWe 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.DiscussionThe 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.

The single-dose Janssen Ad26.COV2.S COVID-19 vaccine elicited robust and persistent anti-spike IgG antibody responses in a 12-month Ugandan cohort

“…Furthermore, breakthrough infections were more frequent among the participants who were S-IgG seronegative at baseline, thus suggesting an advantage of multiple antigenic exposure in eliciting protective vaccine-induced antibodies. Our findings also align with responses elicited by other COVID-19 vaccines used in this demographic, such as Sinovac Biotech’s CoronaVac COVID-19 vaccine ( 30 ), the Oxford/AstraZeneca ChadOx1-S COVID-19 vaccine ( 31 ), the Pfizer-BioNTech BNT162b2 Vaccine ( 24 ), and Moderna’s mRNA 1273 ( 25 ) collectively supporting the vaccine’s effectiveness in this landscape and could have implications for future vaccination and public health strategies ( 32 – 34 ).…”

“…This surge in N-IgG and N-IgM levels, contrary to the vaccine's target on the spike protein, implies potential breakthrough infections (3). These findings inform post-vaccination infection rates and underscore the importance of continuous serological surveillance to guide booster (24)vaccinations. The observed 13% breakthrough rate (8 out of 60) post-Janssen vaccine administration closely mirrors the 10% rate (6 out of 60) reported in comparative studies using the Coronavac COVID-19 vaccine (Sinovac) within the same demographic cohort during the concurrent period (1).…”

“…The observed 13% breakthrough rate (8 out of 60) post-Janssen vaccine administration closely mirrors the 10% rate (6 out of 60) reported in comparative studies using the Coronavac COVID-19 vaccine (Sinovac) within the same demographic cohort during the concurrent period ( 1 ). Recent studies have demonstrated comparable trends for Pfizer-BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccines, with breakthrough rates of 23% (11 of 48) and 16% (3 of 19), respectively ( 24 , 25 ). However, these comparisons should be interpreted cautiously due to the small sample sizes involved.…”