Functional O-specific polysaccharide-specific antibody responses in young children following Shigella infection in Bangladesh
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Cell Reports Medicine
Authors: Biana Bernshtein, Julia A. Zhiteneva, Jeshina Janardhanan, Chanchal Wagh, Meagan Kelly, Smriti Verma, Christina S. Faherty, Angel Nikolov, Wonyeong Jung, Salima Raiyan Basher, Mohammad Ashraful Amin, Shakil Mahamud, Nazmul Hasan Rajib, Fahima Chowdhury, Ashraful Islam Khan, Richelle C. Charles, Peng Xu, Pavol Kováč, Subhra Chakraborty, Robert W. Kaminski, Galit Alter, Taufiqur R. Bhuiyan, Firdausi Qadri, Edward T. Ryan
Institutions: Tel Aviv University, Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard University, International Centre for Diarrhoeal Disease Research, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Johns Hopkins University, Massachusetts Institute of Technology
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: U.S. Department of Defense, Massachusetts General Hospital, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Weizmann Institute of Science, International Centre for Diarrhoeal Disease Research, Bangladesh, National Institutes of Health, Uniformed Services University of the Health Sciences, National Institute of Allergy and Infectious Diseases, Fogarty International Center, Walter Reed Army Institute of Research
Awards: G1651546940, G9000377545, G9000382498, G9000384576, Shigella Conjugate Vaccine (SCV4) Development, Characterization, and Pre-clinical Evaluation, The impact of non-dysentery Shigella-associated diarrhea in children, Functional profiling of OSP-specific and other antibodies during shigella infection, International research training program in vaccine development and public health
OpenAlex ID: W7214229934