Journal
SCIENCE
Volume 328, Issue 5979, Pages 745-748Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1185181
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Funding
- Medical Research Council, UK
- Wellcome Trust, UK
- National Institute for Health Research Biomedical Research Centre
- Thailand Tropical Disease Research Program T2
- Thailand National Centre for Genetic Engineering and Biotechnology
- Medical Research Council [G0600000] Funding Source: researchfish
- MRC [G0400720, G0801508, G0600000] Funding Source: UKRI
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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.
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