Cholera remains a major public health challenge in low-resource settings, including Zambia, where oral cholera vaccines (OCVs) are widely used for outbreak control. Despite their demonstrated effectiveness, the early immunological mechanisms underlying vaccine-induced protection remain incompletely defined, particularly in endemic African populations. Given the central role of cytokines in coordinating immune responses, this study aimed to characterize short-term cytokine dynamics following administration of the Euvichol OCV. In this exploratory prospective cohort study involving 20 healthy adults (15 vaccinated with a single dose of Euvichol; 5 unvaccinated controls) were followed over 14 days. Serum cytokine concentrations were measured at baseline (Day 0) and Day 14 using a multiplex immunoassay platform. Among the eleven cytokines assessed, IL-21 and B-cell activating factor (BAFF) demonstrated significant increases over time within the vaccinated group ( p = 0.002 and p = 0.024, respectively), with corresponding between-group differences at Day 14. Fold-change analysis further confirmed IL-21 as the most upregulated cytokine (effect size r = 0.93), alongside moderate increases in BAFF and other pro-inflammatory mediators. In contrast, most cytokines remained unchanged, and IL-10 showed relative downregulation, indicating the absence of a broad anti-inflammatory response. No meaningful temporal changes were observed in the control group. Not applicable.
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