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Updated: Jun 11, 2025
A High-throughput Shigella-specific Bactericidal Assay
Published on: February 27, 2019
Limited O-specific polysaccharide (OSP)-specific functional antibody responses in young children with Shigella
Insights
Young children develop weaker antibody responses to Shigella infection, hindering innate immune cell activation and increasing disease severity. This highlights a critical gap in protection against shigellosis in endemic areas.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Shigellosis is a major cause of childhood diarrhea deaths globally, with no effective vaccine currently available.
- Existing vaccine candidates have shown limited efficacy in young children, particularly in endemic regions.
- Understanding protective immune responses against Shigella in young children is crucial for vaccine development.
Purpose of the Study:
- To define Shigella-specific antibody responses in young children compared to older individuals in a Shigella-endemic area.
- To investigate functional antibody profiles, including Fc receptor (FcR) binding and innate immune cell activation.
- To identify correlates of protection against Shigella infection and severe shigellosis in different age groups.
Main Methods:
- Functional antibody profiling of Shigella-specific antibody isotypes, FcR binding, and antibody-mediated innate immune cell activation.
- Analysis of longitudinal serum samples from culture-confirmed shigellosis patients (children and older individuals) in Bangladesh.
- Assessment of antibody responses against O-specific polysaccharide (OSP) and protein antigens of Shigella.
Main Results:
- Higher initial Shigella OSP-specific and protein-specific IgG and FcγR binding levels correlated with less severe disease across all ages.
- Children under 5 years exhibited less robust, functional, and durable antibody responses compared to older individuals.
- Functional *S. flexneri* 2a OSP-specific responses, promoting monocyte phagocytosis and activation, were significantly induced only in individuals over 5 years old.
Conclusions:
- Young children with shigellosis mount antibody responses that inadequately activate monocytes, potentially impairing innate immune clearance.
- The limited functional antibody response in young children may contribute to increased susceptibility to severe shigellosis.
- Targeting mechanisms to enhance innate cell activation, particularly polymorphonuclear cell recruitment, could be key for effective Shigella vaccines in young children.
Abstract:
Shigellosis is the second leading cause of diarrheal death in children younger than five years of age globally. At present, there is no broadly licensed vaccine against shigella infection. Previous vaccine candidates have failed at providing protection for young children in endemic settings. Improved understanding of correlates of protection against Shigella infection and severe shigellosis in young children living in endemic settings is needed. 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, a Shigella endemic area. We analyzed Shigella-specific antibody isotypes, FcR binding and antibody-mediated innate immune cell activation in longitudinal serum samples collected at clinical presentation and up to 1 year later. We found that higher initial Shigella O-specific polysaccharide (OSP)-specific and protein-specific IgG and FcγR binding levels correlated with less severe disease regardless of patient age, but that individuals under 5 years of age developed a less prominent class switched, FcR-binding, functional and durable antibody response against both OSP and protein Shigella antigens than older individuals. Focusing on the largest cohort, we found that functional S. flexneri 2a OSP-specific responses were significantly induced only in individuals over age 5 years, and that these responses promoted monocyte phagocytosis and activation. Our findings suggest that in a Shigella endemic region, young children with shigellosis harbor a functional antibody response that fails to maximally activate monocytes; such a response may be important in facilitating subsequent innate cell clearance of Shigella, especially via recruitment and activation of polymorphonuclear cells capable of directly killing Shigella.
