title: Dengue virus infection-enhancing activity in serum samples with neutralizing activity as determined by using FcγR-expressing cells.
abstract: BACKGROUND
  Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhancing activity, may better reflect the biological properties of antibodies in vivo.
  
  
  RESULTS
  We evaluated serum samples from 80 residents of a dengue endemic country, Malaysia, for neutralizing activity, and infection-enhancing activity at 1∶10 serum dilution by using FcγR-negative BHK cells and FcγR-expressing BHK cells. The serum samples consisted of a panel of patients with acute DENV infection (31%, 25/80) and a panel of donors without acute DENV infection (69%, 55/80). A high proportion of the tested serum samples (75%, 60/80) demonstrated DENV neutralizing activity (PRNT(50)≥10) and infection-enhancing activity. Eleven of 18 serum samples from patients with acute secondary DENV infection demonstrated neutralizing activity to the infecting serotype determined by using FcγR-negative BHK cells (PRNT(50)≥10), but not when determined by using FcγR-expressing cells.
  
  
  CONCLUSIONS
  Human serum samples with low neutralizing activity determined by using FcγR-negative cells showed DENV infection-enhancing activity using FcγR-expressing cells, whereas those with high neutralizing activity determined by using FcγR-negative cells demonstrate low or no infection-enhancing activity using FcγR-expressing cells. The results suggest an inverse relationship between neutralizing antibody titer and infection-enhancing activity, and that neutralizing activity determined by using FcγR-expressing cells, and not the activity determined by using FcγR-negative cells, may better reflect protection to DENV infection in vivo.
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Meng Ling
authors.initials: ML
authors.lastname: Moi
authors.forename: Chang-Kweng
authors.initials: CK
authors.lastname: Lim
authors.forename: Kaw Bing
authors.initials: KB
authors.lastname: Chua
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Takasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008296:Malaysia; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000276:immunology; D044967:Serum / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D017452:Receptors, IgG