Development of antibody biomarkers of long term and recent dengue virus infections

J Virol Methods. 2018 Jul:257:62-68. doi: 10.1016/j.jviromet.2018.04.009. Epub 2018 Apr 21.

Abstract

Dengue virus (DENV) infections elicit antibody responses to the non-structural protein 1 (NS1) that are associated with protection against disease. However, the antibody isotypes and subclasses involved, and their kinetics have not been extensively studied. We characterized the antibody responses to DENV NS1 by enzyme-linked immunosorbent assay (ELISA) in a longitudinal cohort of 266 confirmed dengue cases in Recife, Northeast Brazil. Samples were collected during the febrile phase and up to over 3 years after onset of symptoms. The antibodies investigated [IgA, IgM, total IgG (all subclasses measured together) and each subclass (IgG2, IgG3 and IgG4) measured separately] had distinct kinetic profiles following primary or secondary DENV infections. Of interest, most of these antibodies were consistently detected greater than 6 months after onset of symptoms, except for IgG3. Anti-dengue NS1-specific IgG was consistently detected from the acute phase to beyond 3 years after symptom onset. In contrast, anti-dengue NS1-specific IgG3 was detected within the first week, peaked at week 2-3, and disappeared within 4-6 months after onset of symptoms. The mean duration of the IgG3 positive signal was 149 days (ranging from 126 to 172 days). In conclusion, anti-dengue NS1-specific IgG and IgG3 are potential biomarkers of long-term and recent (less than 6 months) DENV infections, respectively.

Keywords: Antibody; Biomarker; IgG subclasses; IgG3; Long term; Recent infection; Virus exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Biomarkers / blood*
  • Brazil
  • Child
  • Child, Preschool
  • Dengue / diagnosis*
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Time Factors
  • Viral Nonstructural Proteins / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Viral Nonstructural Proteins