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

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 matu...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-53916-9
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author 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
author_facet 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
author_sort Camila D. Odio
collection DOAJ
description 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.
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spelling doaj-art-8e168c39396146e0921752c74b3e766e2025-01-05T12:37:14ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-024-53916-9Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protectiveCamila D. Odio0Jedas Veronica Daag1Maria Vinna Crisostomo2Charlie J. Voirin3Ana Coello Escoto4Cameron Adams5Lindsay Dahora Hein6Rosemary A. Aogo7Patrick I. Mpingabo8Guillermo Raimundi Rodriguez9Saba Firdous10Maria Abad Fernandez11Laura J. White12Kristal An Agrupis13Jacqueline Deen14Aravinda M. de Silva15Michelle Ylade16Leah C. Katzelnick17Viral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInstitute of Child Health and Human Development, National Institutes of Health, University of the Philippines ManilaInstitute of Child Health and Human Development, National Institutes of Health, University of the Philippines ManilaViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Microbiology and Immunology, University of North Carolina School of MedicineDepartment of Microbiology and Immunology, University of North Carolina School of MedicineViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Microbiology and Immunology, University of North Carolina School of MedicineDepartment of Microbiology and Immunology, University of North Carolina School of MedicineInstitute of Child Health and Human Development, National Institutes of Health, University of the Philippines ManilaInstitute of Child Health and Human Development, National Institutes of Health, University of the Philippines ManilaDepartment of Microbiology and Immunology, University of North Carolina School of MedicineInstitute of Child Health and Human Development, National Institutes of Health, University of the Philippines ManilaViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract 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.https://doi.org/10.1038/s41467-024-53916-9
spellingShingle 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
Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
Nature Communications
title Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
title_full Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
title_fullStr Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
title_full_unstemmed Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
title_short Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective
title_sort dengue virus igg and neutralizing antibody titers measured with standard and mature viruses are protective
url https://doi.org/10.1038/s41467-024-53916-9
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