Antibody kinetics following confirmed Shigella infection: A longitudinal study in Dhaka, Bangladesh.

BACKGROUND: Shigella causes an estimated 200 million infections annually, disproportionately affecting children in low- and middle-income countries. Accurate incidence measurement is hindered by brief pathogen shedding and limited diagnostics. Serological approaches can detect infections missed by clinical surveillance but require well-characterized post-infection antibody kinetics. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed archived sera from the Study of Shigella Antibody Responses (SOSAR), a longitudinal cohort of 48 individuals with culture- or molecular-confirmed Shigella infection in Dhaka, Bangladesh (2021-2022). IgG and IgA responses to five antigens (IpaB and the O-specific polysaccharides [OSP] of S. flexneri 2a, 3a, and 6, and S. sonnei ) were measured at baseline and approximately 7, 30, 90, and 180 days post-infection by multiplex bead-based immunoassay, and modeled with a two-phase rise-peak-decay model in a Bayesian hierarchical framework. We compared three estimation approaches: pooled (all infections), serotype-specific (serotype-matched only), and combined S. flexneri (2a and 3a, leveraging cross-reactivity). IgA rose rapidly and returned toward baseline within 2- 3 months across all antigens, whereas IgG remained elevated above baseline throughout 200 days. Children under five showed lower baselines and higher peaks (primary infection); older children showed higher baselines and lower peaks (prior exposure). IpaB responses were elevated across all serotypes, whereas OSP responses were serotype-restricted, with cross-reactivity between S. flexneri 2a and 3a. CONCLUSIONS/SIGNIFICANCE: Shigella antibody kinetics are isotype-, antigen-, serotype-, and age-dependent. IgA marks recent infection; IgG reflects longer-term exposure. Pooling antigenically distinct serotypes ( S. sonnei ) caused convergence failures, whereas serotype-matched estimation recovered biologically plausible decay. These parameters provide foundational inputs for seroepidemiologic tools and seroincidence estimation in Shigella -endemic settings. AUTHOR SUMMARY: Shigella is a leading cause of diarrhea and death in young children, especially in low- resource settings where laboratory diagnosis is limited. Because the bacteria are difficult to detect directly, measuring antibodies in the blood is a promising way to identify people who have recently been infected - but this requires knowing how antibody levels rise and fall after infection. We followed 48 people with confirmed Shigella infection in Dhaka, Bangladesh, for up to 200 days and tracked their IgG and IgA antibody responses to several Shigella antigens. We found that IgA rose quickly and faded within a few months, whereas IgG remained elevated much longer, and that responses depended on the infecting serotype. These antibody kinetics provide the foundation for tools to estimate how often Shigella infections occur in a community - information that can guide surveillance, vaccine evaluation, and public-health decisions where the burden is greatest.