title: Antibody avidity following secondary dengue virus type 2 infection across a range of disease severity.
abstract: BACKGROUND
  The four dengue virus serotypes (DENV1-4) are responsible for the most prevalent mosquito-borne viral illness in humans. DENV causes a spectrum of disease from self-limiting dengue fever (DF) to severe, life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Antibodies from one infection can contribute to either protection or increased disease severity in a subsequent infection with a distinct DENV serotype. The effectiveness of the antibody response is modulated by both the affinity and avidity of the antibody/antigen interaction.
  
  
  OBJECTIVE
  We investigated how antibody avidity developed over time following secondary DENV2 infection across different disease severities.
  
  
  METHODS
  We analyzed sera from 42 secondary DENV2-infected subjects (DF, n=15; DHF, n=16; DSS, n=11) from a pediatric hospital-based dengue study in Nicaragua. IgG avidity against DENV2 virions was measured in samples collected during acute and convalescent phases as well as 3, 6, and 18 months post-illness using a urea enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The data show a significant increase in avidity from acute to convalescent phase followed by a decrease from convalescent phase to 3 months post-symptom onset, then a plateau. Linear regression analysis comparing antibody avidity between disease severity groups over time indicate that individuals with more severe disease (DHF/DSS) experienced greater decay in antibody avidity over time compared to less severe disease (DF), and ROC curve analysis showed that at 18 months post-illness, lower avidity was associated with previously having experienced more severe disease.
  
  
  CONCLUSIONS
  These data suggest that increased dengue disease severity is associated with lower antibody avidity at later time-points post-illness.
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Lau
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Green
authors.affiliation: Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministerio de Salud, Managua, Nicaragua.
authors.forename: Angel
authors.initials: A
authors.lastname: Balmaseda
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, USA. Electronic address: eharris@berkeley.edu.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000276:immunology*; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D008297:Male; D009527:Nicaragua; D065288:Serogroup; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G
keywords: Antibody avidity; Dengue hemorrhagic fever/dengue shock syndrome; Dengue virus; Disease severity