Anti-Nonstructural Protein 1 Antibody Kinetics and Their Association With Disease Severity in Pediatric Dengue

Abstract

Background. Dengue is an immune-mediated disease with severe manifestations often linked to secondary infections. Dengue virus nonstructural protein 1 (DENV NS1) and corresponding antibodies are thought to play a crucial role in disease pathogenesis. Methods. This study investigated the kinetics of anti-NS1 antibody responses in relation to NS1 levels and NS1 immune complexes (ICs) in pediatric dengue patients with varying disease severity following secondary DENV infections with all four serotypes, using retrospective plasma samples collected in Thailand and analyzed by enzyme-linked immunosorbent assays (ELISAs). Plasma samples from pediatric patients with other febrile illnesses (OFI) and healthy adults served as non-dengue control groups. Results. Anti-NS1 IgG (particularly IgG1 and IgG4) and IgA persisted for at least 6 months after illness and were associated with increased dengue severity, whereas the shorter-lived anti-NS1 IgM was higher in patients with milder dengue. Anti-NS1 IgG also persisted notably longer than anti-DENV IgG. Anti-NS1 IgG3 showed a transient surge across all four serotypes, suggesting its potential as a marker of recent infection. NS1 proteins and NS1 ICs were positively correlated, inversely related to anti-NS1 IgG, and strongly associated with severe dengue. Conclusions. Anti-NS1 antibody isotypes and IgG subclasses exhibited distinct associations with dengue severity, influenced by both infecting serotypes and time since illness onset. Correlations among NS1, anti-NS1 antibodies, and NS1 ICs were observed during the acute phase of secondary infection, potentially influencing dengue disease outcomes. These findings enhance our understanding of dengue immunopathogenesis and may inform improved diagnostic and surveillance tools. © The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.