title: Cross-reacting antibodies enhance dengue virus infection in humans.
abstract: Dengue virus co-circulates as four serotypes, and sequential infections with more than one serotype are common. One hypothesis for the increased severity seen in secondary infections is antibody-dependent enhancement (ADE) leading to increased replication in Fc receptor-bearing cells. In this study, we have generated a panel of human monoclonal antibodies to dengue virus. Antibodies to the structural precursor-membrane protein (prM) form a major component of the response. These antibodies are highly cross-reactive among the dengue virus serotypes and, even at high concentrations, do not neutralize infection but potently promote ADE. We propose that the partial cleavage of prM from the viral surface reduces the density of antigen available for viral neutralization, leaving dengue viruses susceptible to ADE by antibody to prM, a finding that has implications for future vaccine design.
authors.affiliation: Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Wanwisa
authors.initials: W
authors.lastname: Dejnirattisai
authors.forename: Amonrat
authors.initials: A
authors.lastname: Jumnainsong
authors.forename: Naruthai
authors.initials: N
authors.lastname: Onsirisakul
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitton
authors.forename: Sirijitt
authors.initials: S
authors.lastname: Vasanawathana
authors.forename: Wannee
authors.initials: W
authors.lastname: Limpitikul
authors.forename: Chunya
authors.initials: C
authors.lastname: Puttikhunt
authors.forename: Carolyn
authors.initials: C
authors.lastname: Edwards
authors.forename: Thaneeya
authors.initials: T
authors.lastname: Duangchinda
authors.forename: Sunpetchuda
authors.initials: S
authors.lastname: Supasa
authors.forename: Kriangkrai
authors.initials: K
authors.lastname: Chawansuntati
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolsapaya
authors.forename: Gavin
authors.initials: G
authors.lastname: Screaton
mesh_terms: D000330:Aedes; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology*; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology* / Q000502:physiology; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D009000:Monocytes / Q000276:immunology / Q000821:virology; D011961:Receptors, Fc / Q000276:immunology; D012703:Serotyping; D020298:U937 Cells; D014759:Viral Envelope Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; D011961:Receptors, Fc; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins
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