Comparative analysis of serum antibody responses and immune landscapes in patients with acute DENV-1, DENV-2, and Chikungunya virus infections

Introduction Dengue virus (DENV) and chikungunya virus (CHIKV) are major mosquito-borne arboviruses that increasingly co-circulate in tropical and subtropical regions, including southern China. However, the extent to which these viruses induce shared or distinct host immune responses remains poorly understood. This study aimed to comparatively characterize immune responses during acute DENV-1, DENV-2, and CHIKV infections. Materials and methods A total of 80 serum samples were analyzed, including 65 samples from patients with laboratory-confirmed DENV-1 (n = 29), DENV-2 (n = 10), or CHIKV (n = 26) infections and 15 healthy controls.Viral RNA was detected by real-time reverse transcription polymerase chain reaction. Virus-specific IgM and IgG responses were measured by Enzyme-Linked Immunosorbent Assay, and serum cytokines were quantified using a multiplex assay. Group comparisons used nonparametric tests, and associations among antibody responses, cytokine concentrations, and viral RNA levels were assessed using Spearman’s rank correlation. Multiple comparisons were adjusted using the Benjamini-Hochberg (BH) procedure. Results The three infections shared features of interferon-associated immune activation and relatively restrained systemic inflammation but exhibited distinct immune mediator profiles, characterized by differential inflammatory mediator and growth factor responses. After multiple-testing correction, cytokine–cytokine correlation analysis revealed both shared and infection-specific patterns of immune mediator covariation, with shared associations involving IL-9, TNF-β, CCL4, and CXCL1 across all three infection groups. Positive associations between pathogen-specific IgM responses and Ct values were observed across the infections, although the association was not statistically significant for DENV-2 after multiple-testing correction. IgG responses showed a similar association only in DENV-1 infection. Integration of cytokine and antibody profiles further revealed distinct immune association patterns: DENV-1 showed broader associations involving viral RNA levels, inflammatory mediators, and humoral responses, whereas CHIKV displayed a more restricted pattern centered on associations between inflammatory mediators and IgM responses. Discussion These findings reveal shared and distinct immune responses during acute DENV-1, DENV-2, and CHIKV infections and provide a comparative framework for investigating virus-associated immune regulation during acute arboviral infections.