Long-Term Antibody Responses to Vibrio cholerae Across Natural Infection, Vaccination, and Challenge: A Systematic Review.

BACKGROUND

Cholera 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.

METHODS

We systematically reviewed literature from 1980 to 2025 containing longitudinal antibody measurements in humans following exposure to Vibrio cholerae O1/O139 and associated vaccines.

RESULTS

51 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.

CONCLUSIONS

This 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 MESSAGES: ur 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. We 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.it 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.