<p>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 (<i>n</i> = 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%, <i>p</i> = 0.007). Serotype-specific antibodies binding EDIII or NS1 had no association with dengue risk. Standard virus PRNT geometric mean titers (GMT) &gt; 200 and mature GMT &gt; 100 were associated with reduced dengue disease overall (<i>p</i> &lt; 0.01). High DENV2 and DENV3 titers against either standard or mature viruses protected against the matched serotype (<i>p</i> &lt; 0.01). While 43% of dengue cases had standard virus PRNT titers&gt;100, only 2% of cases had mature virus PRNT titers&gt;100 (<i>p</i> &lt; 0.001), indicating a lower, more consistent threshold for protection. These assays may serve as correlates of protection.</p>

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Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective

  • Camila D. Odio,
  • Jedas Veronica Daag,
  • Maria Vinna Crisostomo,
  • Charlie J. Voirin,
  • Ana Coello Escoto,
  • Cameron Adams,
  • Lindsay Dahora Hein,
  • Rosemary A. Aogo,
  • Patrick I. Mpingabo,
  • Guillermo Raimundi Rodriguez,
  • Saba Firdous,
  • Maria Abad Fernandez,
  • Laura J. White,
  • Kristal An Agrupis,
  • Jacqueline Deen,
  • Aravinda M. de Silva,
  • Michelle Ylade,
  • Leah C. Katzelnick

摘要

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.