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Introduction: The study investigation examined the immune response to the Janssen Ad26.COV2.S COVID-19 vaccine within a Ugandan cohort, specifically targeting antibodies directed against spike (S) and nucleocapsid (N) proteins. We aimed to examine the durability and robustness of the induced antibody response while also assessing occurrences of breakthrough infections and previous anti-Spike seropositivity to SARS-CoV-2., Methods: The study included 319 specimens collected over 12 months from 60 vaccinees aged 18 to 64. Binding antibodies were quantified using a validated ELISA method to measure SARS-CoV-2-specific IgG, IgM, and IgA levels against the S and N proteins., Results: The results showed that baseline seropositivity for S-IgG was high at 67%, increasing to 98% by day 14 and consistently stayed above 95% for up to 12 months. However, S-IgM responses remained suboptimal. A raised S-IgA seropositivity rate was seen that doubled from 40% at baseline to 86% just two weeks following the initial vaccine dose, indicating sustained and robust peripheral immunity. An increase in N-IgG levels at nine months post-vaccination suggested breakthrough infections in eight cases. Baseline cross-reactivity influenced spike-directed antibody responses, with individuals harbouring S-IgG antibodies showing notably higher responses., Discussion: Robust and long lasting vaccine and infection-induced immune responses were observed, with significant implications for regions where administering subsequent doses poses logistical challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Serwanga, Kato, Oluka, Ankunda, Sembera, Baine, Kitabye, Namuyanja, Opio, Katende, Ejou, The COVID-19 Immunoprofiling Team and Kaleebu.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ankunda, Katende, Oluka, Sembera, Baine, Odoch, Ejou, Kato, and The COVID-19 Immunoprofiling Team, Kaleebu and Serwanga.)

Introduction: This study sought to elucidate the long-term antibody responses to the Moderna mRNA-1273 COVID-19 vaccine within a Ugandan cohort, aiming to contribute to the sparse data on m-RNA vaccine immunogenicity in Sub-Saharan Africa., Methods: We tracked the development and persistence of the elicited antibodies in 19 participants aged 18 to 67, who received two doses of the mRNA-1273 vaccine. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibodies against the spike (S) and nucleoproteins (N). The study's temporal scope extended from the baseline to one year, capturing immediate and long-term immune responses. Statistical analyses were performed using the Wilcoxon test to evaluate changes in antibody levels across predetermined intervals with the Hochberg correction for multiple comparisons., Results: Our results showed a significant initial rise in spike-directed IgG (S-IgG) and spike-directed IgA (S-IgA) levels, which remained elevated for the duration of the study. The S-IgG concentrations peaked 14 days afterboosting, while spike-directed IgM (S-IgM) levels were transient, aligning with their early response role. Notably, post-booster antibody concentrations did not significantly change. Prior S-IgG status influenced the post-priming S-IgA dynamics, with baseline S-IgG positive individuals maintaining higher S-IgA responses, a difference that did not reach statistical difference post-boost. Three instances of breakthrough infections: two among participants who exhibited baseline seropositivity for S-IgG, and one in a participant initially seronegative for S-IgG., Discussion: In conclusion, the mRNA-1273 vaccine elicited robust and persistent S-IgG and S-IgA antibody responses, particularly after the first dose, indicating potential for long-term immunity. Prior viral exposure enhances post-vaccination S-IgA responses compared to naive individuals, which aligned with the prior-naïve, post-boost. The stable antibody levels observed post-booster dose, remaining high over an extended period, with no significant secondary rise, and no difference by baseline exposure, suggest that initial vaccination may sufficiently prime the immune system for prolonged protection in this population, allowing for potential to delay booster schedules as antibody responses remained high at the time of boosting. This finding calls for a reassessment of the booster dose scheduling in this demographic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Serwanga, Ankunda, Katende, Baine, Oluka, Odoch, Nantambi, Mugaba, Namuyanja, Ssali, Ejou, Kato, The COVID-19 Immunoprofiling Team, Musenero and Kaleebu.)

Introduction: This study investigated the antibody responses to the inactivated COVID-19 vaccine, CoronaVac (Sinovac Biotech) in the African population to provide valuable insights into long-term immunity and breakthrough infections against SARS-CoV-2 in individuals with varying prior IgG seropositivity., Methods: Real-life cohorts were used to longitudinally track antibody levels against the SARS-CoV-2 spike and nucleoprotein in 60 participants over 12 months to examine the levels of multiple antibody isotypes (S-IgG, S-IgM, S-IgA, N-IgG, and N-IgM)., Results: Throughout the 12 months, we observed consistently high and stable seropositivity rates for spike-IgG antibodies, spike-IgM antibodies showed a decline in frequencies over time, and spike-IgA levels remained moderate and stable. Vaccinated individuals previously positive for spike-IgG antibodies demonstrated strong and persistent seropositivity, while those initially negative experienced a gradual and delayed increase in seropositivity rates. The fold change analysis of S- and N- antibody responses demonstrated a consistently stable and comparable profile over time, indicating that vaccine-induced antibody responses remain constant and lack significant fluctuations beyond the initial boost. The study emphasized that individuals lacking previous IgG positivity showed reduced vaccine-induced spike-IgG antibodies and were more susceptible to breakthrough infections, highlighting their higher vulnerability. All cases of breakthrough infections were asymptomatic, indicating the conferred protection to the vaccinated individuals., Discussion: The findings corroborated earlier studies on the effectiveness of the CoronaVac vaccine and emphasized the significance of accounting for pre-existing seropositivity in vaccine assessments. This study effectively demonstrated durable antibody responses against SARS-CoV-2 in the African population following the CoronaVac vaccination, providing crucial insights for informing vaccination strategies and safeguarding vulnerable populations. Continuous surveillance is imperative for tracking breakthrough infections and monitoring waning immunity. The insights gained offer crucial direction for public health strategies and enhance comprehension of vaccine effectiveness in sub-Saharan Africa. Further research should explore functional outcomes, cellular immune responses, and the vaccine's effectiveness against different variants to enhance our understanding and optimize vaccine strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sembera, Baine, Ankunda, Katende, Oluka, Akoli, Kato, Odoch, Ejou, Opio, Musenero, The COVID-19 Immunoprofiling Team, Kaleebu and Serwanga.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Serwanga, Baine, Mugaba, Ankunda, Auma, Oluka, Kato, Kitabye, Sembera, Odoch, Ejou, Nalumansi, Gombe, Musenero, Kaleebu and the COVID-19 Immunoprofiling Team.)