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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.

Original publication

DOI

10.1126/science.1185181

Type

Journal article

Journal

Science

Publication Date

07/05/2010

Volume

328

Pages

745 - 748

Keywords

Aedes, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antibody-Dependent Enhancement, Antigens, Viral, Cell Line, Cross Reactions, Dengue, Dengue Vaccines, Dengue Virus, Encephalitis Virus, Japanese, Humans, Immune Evasion, Monocytes, Receptors, Fc, Serotyping, U937 Cells, Viral Envelope Proteins, Viral Matrix Proteins, Virus Replication