The supplementary materials for the study "Antibody-dependent enhancement of severe dengue disease in humans" include detailed methods, figures, and tables supporting the research. The Pediatric Dengue Cohort Study (PDCS) involved 6,684 children aged 2–14 years, with annual blood samples collected to measure DENV-specific antibodies using an Inhibition ELISA (iELISA). The iELISA measures the ability of antibodies to block DENV antigen binding, providing titers that are compared to other assays like hemagglutination inhibition (HI) and plaque reduction neutralization test (PRNT). The iELISA is a sensitive, high-throughput method that is widely used for DENV case identification and seroprevalence studies. The study characterized DENV antigens and used a panel of monoclonal antibodies (mAbs) to assess epitopes recognized by the iELISA. It found that the iELISA primarily measures antibodies binding to cross-reactive epitopes, some of which are associated with antibody-dependent enhancement (ADE). The study also analyzed the relationship between iELISA titers and neutralizing antibody titers, finding strong correlations with neutralizing titers for DENV1-4. Dengue cases were classified as severe or non-severe based on clinical criteria, and the study evaluated the impact of pre-existing DENV-Ab titers on disease severity. It found that higher DENV-Ab titers were associated with reduced risk of severe dengue, particularly in the protective range (>1:80). The study also explored the kinetics of DENV-Ab titers over time, finding that children who developed severe dengue had lower titers immediately after infection but similar decay rates over time. Nested case-control analyses were conducted to assess the association between pre-existing DENV-Ab titers and the risk of severe secondary dengue. The study found that higher titers were associated with lower odds of severe disease. The potential implications of ADE on transmission were also discussed, with findings suggesting that ADE may influence viral kinetics and transmission dynamics. The supplementary materials include figures and tables that provide detailed data on iELISA titers, neutralizing antibody titers, and disease outcomes, supporting the main findings of the study. The results highlight the importance of DENV-Ab titers in predicting disease severity and the role of ADE in dengue pathogenesis.The supplementary materials for the study "Antibody-dependent enhancement of severe dengue disease in humans" include detailed methods, figures, and tables supporting the research. The Pediatric Dengue Cohort Study (PDCS) involved 6,684 children aged 2–14 years, with annual blood samples collected to measure DENV-specific antibodies using an Inhibition ELISA (iELISA). The iELISA measures the ability of antibodies to block DENV antigen binding, providing titers that are compared to other assays like hemagglutination inhibition (HI) and plaque reduction neutralization test (PRNT). The iELISA is a sensitive, high-throughput method that is widely used for DENV case identification and seroprevalence studies. The study characterized DENV antigens and used a panel of monoclonal antibodies (mAbs) to assess epitopes recognized by the iELISA. It found that the iELISA primarily measures antibodies binding to cross-reactive epitopes, some of which are associated with antibody-dependent enhancement (ADE). The study also analyzed the relationship between iELISA titers and neutralizing antibody titers, finding strong correlations with neutralizing titers for DENV1-4. Dengue cases were classified as severe or non-severe based on clinical criteria, and the study evaluated the impact of pre-existing DENV-Ab titers on disease severity. It found that higher DENV-Ab titers were associated with reduced risk of severe dengue, particularly in the protective range (>1:80). The study also explored the kinetics of DENV-Ab titers over time, finding that children who developed severe dengue had lower titers immediately after infection but similar decay rates over time. Nested case-control analyses were conducted to assess the association between pre-existing DENV-Ab titers and the risk of severe secondary dengue. The study found that higher titers were associated with lower odds of severe disease. The potential implications of ADE on transmission were also discussed, with findings suggesting that ADE may influence viral kinetics and transmission dynamics. The supplementary materials include figures and tables that provide detailed data on iELISA titers, neutralizing antibody titers, and disease outcomes, supporting the main findings of the study. The results highlight the importance of DENV-Ab titers in predicting disease severity and the role of ADE in dengue pathogenesis.