title: Low levels of antibody-dependent enhancement in vitro using viruses and plasma from dengue patients.
abstract: BACKGROUND
  The majority of dengue patients infected with any serotype of dengue virus (DENV) are asymptomatic, but the remainder may develop a wide spectrum of clinical symptoms, ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). Severe cases occur more often in patients who experience a secondary infection with a different virus serotype. A phenomenon called antibody-dependent enhancement (ADE) has been proposed to explain the onset of these severe cases, but the exact mechanism of ADE remains unclear.
  
  
  RESULTS
  Virus neutralization and ADE assays were performed using ultracentrifugation supernatants of acute-phase sera from patients with secondary infections or human monoclonal antibodies (HuMAbs) as anti-DENV antibodies. Virus sources included infectious serum-derived viruses from the ultracentrifugation precipitates, laboratory-culture adapted DENV, or recombinant DENVs derived from patient sera. In contrast to the high levels of ADE observed with laboratory virus strains, low ADE was observed with autologous patient-derived viruses, when patient sera were used to provide the antibody component in the ADE assays. Similar results were obtained using samples from DF and DHF patients. Recombinant-viruses derived from DHF patients showed only minor differences in neutralization and ADE activity in the presence of HuMAbs or plasma derived from the same DHF patient.
  
  
  CONCLUSIONS
  Serum or plasma taken from patients during the acute phase of a secondary infection showed high levels of ADE, but no neutralization activity, when assayed in the presence of laboratory-adapted virus strains. By contrast, serum or plasma from the same patient showed high levels of neutralization activity but failed to induce significant ADE when the assays were performed with autologous virus. These results demonstrate the significance of the virus source when measuring ADE. They also suggest that repeated passage of DENV in cell culture has endowed it with the capacity to induce high levels of ADE.
authors.affiliation: Mahidol-Osaka Center for Infectious Diseases (MOCID), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Panjaporn
authors.initials: P
authors.lastname: Chaichana
authors.affiliation: Mahidol-Osaka Center for Infectious Diseases (MOCID), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
authors.affiliation: Mahidol-Osaka Center for Infectious Diseases (MOCID), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Orapim
authors.initials: O
authors.lastname: Puiprom
authors.affiliation: Mahidol-Osaka Center for Infectious Diseases (MOCID), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Sasayama
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Center of Excellence for Antibody Research (CEAR), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Pongrama
authors.initials: P
authors.lastname: Ramasoota
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D002522:Chlorocebus aethiops; D060085:Coinfection / Q000097:blood / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D009500:Neutralization Tests; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology*; D019595:Severe Dengue / Q000097:blood / Q000276:immunology* / Q000821:virology; D012720:Severity of Illness Index; D014709:Vero Cells
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007106:Immune Sera