Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus

Am J Trop Med Hyg. 2015 Feb;92(2):370-6. doi: 10.4269/ajtmh.14-0455. Epub 2014 Dec 29.

Abstract

Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigen-Antibody Complex / immunology*
  • Callithrix / immunology
  • Callithrix / virology
  • Cross Reactions / immunology
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Immunization, Passive
  • Receptors, IgG / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Viral Plaque Assay
  • Viremia / virology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigen-Antibody Complex
  • Receptors, IgG