Abstract
The standard dengue virus (DENV) neutralization assay inconsistently predicts dengue protection. We compare how IgG ELISA, envelope domain III (EDIII), or non-structural protein 1 (NS1) binding antibodies, and titers from plaque reduction neutralization tests (PRNTs) using standard and mature viruses are associated with dengue. The ELISA measures IgG antibodies that bind to inactivated DENV1-4. The EDIII and NS1 assays measure binding antibodies, and the PRNTs measure neutralizing antibodies to each specific DENV serotype. Healthy children (n = 1206) in Cebu, Philippines were followed for 5 years. ELISA IgG≥3 was associated with reduced dengue probability relative to naïve children (3% vs. 10%, p = 0.007). Serotype-specific antibodies binding EDIII or NS1 had no association with dengue risk. Standard virus PRNT geometric mean titers (GMT) > 200 and mature GMT > 100 were associated with reduced dengue disease overall (p < 0.01). High DENV2 and DENV3 titers against either standard or mature viruses protected against the matched serotype (p < 0.01). While 43% of dengue cases had standard virus PRNT titers>100, only 2% of cases had mature virus PRNT titers>100 (p < 0.001), indicating a lower, more consistent threshold for protection. These assays may serve as correlates of protection.