title: Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies.
abstract: Although its underlying mechanisms are poorly understood, data comparing each of the four dengue virus serotypes suggest that in vitro antibody-dependent infection enhancement is a reproducible and measurable phenomenon related to other serological measures of antibody-virus binding. Information characterizing infection enhancement may provide clues to disease pathogenesis for dengue and other viruses that exhibit antibody-enhanced infection. We propose criteria for the detection and quantification of in vitro antibody-dependent enhancement of flavivirus infection based on observations using all four dengue virus serotypes, macrophage-like cell lines and human peripheral blood monocytes, and various immune sera and monoclonal antibodies. It is proposed that antibody-dependent infection enhancement is defined by the following findings: (i) significantly increased virus production is measured in quantitative assays at different points on the growth curve; (ii) assays of the virus output of cells infected with mixtures of constant amounts of virus and serial dilutions of the pre-existing antibody source produce characteristic 'enhancement profiles' of rising and falling virus output over at least a 10(-3)-fold dilution range; (iii) for each enhancing antibody source the dilution producing maximal infection enhancement is related to other serological measures of binding to the envelope, or another virus component; (iv) infection enhancement is detected with different antibody sources and virus strains (when available) tested over a range of m.o.i.; (v) other causes of enhanced virus production are ruled out.
authors: Department of Tropical Medicine and Medical Microbiology, University of Hawaii School of Medicine, Leahi Hospital, Honolulu 96816.
authors: D M
authors: DM
authors: Morens
authors: S B
authors: SB
authors: Halstead
mesh_terms: D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D003716:Dengue Virus / Q000145:classification / Q000254:growth & development / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000276:immunology; D011247:Pregnancy; D012703:Serotyping
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral