Longitudinal Antibody Responses to Vibrio cholerae: A Systematic Review

BackgroundCholera is a critical global health threat, with significant impact on low- and middle-income countries. Clinical surveillance is limited by non-specific symptoms, dependence on care-seeking, and availability of microbiological diagnostics, making burden estimation difficult. Serosurveillance is a potential solution, but the design and interpretation of cross-sectional seroepidemiological studies are currently limited by a lack of knowledge of longitudinal antibody trajectories. MethodsWe systematically reviewed literature from 1980 to 2025 containing longitudinal antibody measurements in humans following exposure to Vibrio cholerae O1/O139 and associated vaccines. Results51 studies representing adults and children from 1 low-income (1 study), 5 lower-middle-income (24 studies), 3 upper-middle-income (5 studies) and 5 high-income (21 studies) countries were included. 16 studies followed natural infection, 36 involved vaccination, and 6 were human challenge models, with some overlap. Antibody responses following infection were significantly higher than those induced by vaccination, particularly against O-specific polysaccharide (OSP). Younger children exhibited higher peak fold-change IgA responses to Cholera-toxin B-subunit (CTB) than older children and adults across infection and vaccine studies. Following vaccination, individuals from high-income countries showed higher IgA, IgG, and vibriocidal fold-change responses compared to those from lower-income settings. Limited data from challenge studies revealed slower decay of IgG compared to IgA and IgM. ConclusionsThis review enhances our understanding of longitudinal immune responses to V. cholerae, highlighting variability in antibody kinetics across age groups, geographic regions, and study designs, and informs the design and interpretation of seroepidemiological studies of cholera. Key MessagesO_LIur Research Question: We aimed to systematically review longitudinal antibody responses in humans following natural infection, vaccination, or challenge with Vibrio cholerae O1/O139, to inform interpretation of cross-sectional seroepidemiologic studies. C_LIO_LIWe Found: We found that antibody responses vary significantly by exposure type, age group, and geographic setting, with infection inducing stronger and longer-lasting responses than vaccination, and younger children showing higher IgA responses to CTB compared to older children and adults. C_LIO_LIit is Important: These findings highlight variability in immune responses across populations and underscore the need for tailored approaches to accurately estimate cholera burden and guide global control strategies. C_LI