Functional O-specific polysaccharide-specific antibody responses in young children following Shigella infection in Bangladesh.

Shigellosis is the second leading cause of diarrheal death in children under 5 years globally, yet no licensed vaccine exists, partly due to poor understanding of protective immunity in young children, especially in endemic settings. Here, we applied a functional antibody-profiling approach to define Shigella-specific antibody responses in young children versus older individuals with culture-confirmed shigellosis in Bangladesh. We found that higher baseline O-specific polysaccharide (OSP)-specific and protein-specific IgG and FcγR binding levels correlated with less severe disease regardless of age. We also found that over time, individuals under 5 years of age developed a less functional and durable response against OSP than older individuals. We demonstrate that OSP-specific IgG increased uptake of live Shigella by monocytes and macrophages in an Fc-dependent mechanism. Our findings suggest that young children develop limited OSP-specific functional antibody responses that fail to maximally involve innate immune cells. Innate cell clearance may be important in protecting against Shigella.