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Journal Article
Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
2025
Overview
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.
Correlates of protection for dengue virus infection and associated disease remain unclear. Here, the authors report results from an observational study in Cebu, Philippines showing that neutralizing antibodies measured using mature dengue viruses have the strongest associations with protection against dengue.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ Antibodies, Neutralizing - blood
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Assaying
/ Binding
/ Child
/ Enzyme-Linked Immunosorbent Assay
/ Female
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin G - immunology
/ Male
/ Science
/ Viral Nonstructural Proteins - immunology
/ Viruses
