Obesity in children is associated with increased dengue virus binding, but not neutralizing, antibody responses following primary infection

Background. Obesity has been associated with higher risk of dengue virus (DENV) infection and disease, yet its influence on antibody responses to DENV remains undefined. Methods. We evaluated whether nutritional status -- based on BMI z-score (BMIz) -- or blood markers of body fat -- leptin and adiponectin --are associated with binding and/or neutralizing antibody responses to DENV in 85 children in the Nicaraguan Pediatric Dengue Cohort Study who experienced a primary DENV infection in 2019. Associations were estimated using linear models adjusting for age, sex, and DENV infection outcome. Results. Compared to children with normal weight, those with obesity had higher quantities of DENV binding antibodies (fold-change [FC] 1.89, 95% confidence interval [CI] 1.02, 3.48) but no difference in neutralizing antibodies. Likewise, leptin concentration was associated with higher quantities of binding antibodies (FC 1.22, 95%CI 1.09, 1.37), while adiponectin was associated with lower quantities (FC 0.79, 95%CI 0.67, 0.94), and neither was associated with neutralizing antibodies. Lower neutralizing efficiency (neutralizing/binding antibodies) was observed in children with obesity (FC 0.67, 95%CI 0.48, 0.93). Conclusions. Our results indicate that obesity is associated with higher antibody quantity (binding) but not higher quality (neutralization) post-primary DENV infection -- implying that antibodies generated by children with obesity have lower neutralization efficiency, requiring greater quantities to reach similar levels of neutralization than children with normal weight. Further, the agreement among the three models using distinct proxies of body fat -- BMIz, leptin, and adiponectin -- demonstrates that adipokines are useful in supplementing BMIz analysis or as independent predictors of immune responses.