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Science 328 (5979): 745-748

Copyright © 2010 by the American Association for the Advancement of Science

Cross-Reacting Antibodies Enhance Dengue Virus Infection in Humans

Wanwisa Dejnirattisai,1 Amonrat Jumnainsong,1 Naruthai Onsirisakul,1,2 Patricia Fitton,1 Sirijitt Vasanawathana,3 Wannee Limpitikul,4 Chunya Puttikhunt,5 Carolyn Edwards,1 Thaneeya Duangchinda,5 Sunpetchuda Supasa,6 Kriangkrai Chawansuntati,1 Prida Malasit,5,6 Juthathip Mongkolsapaya,1,6,*,{dagger} Gavin Screaton1,*,{dagger}

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.

1 Department of Medicine, Imperial College London, London W12 0NN, UK.
2 Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
3 Pediatric Department, Khon Kaen Hospital, Khon Kaen 4000, Thailand.
4 Pediatric Department, Songkhla Hospital, Songkhla 90100, Thailand.
5 BIOTEC, NSTDA, Phatumthani 12120, Thailand.
6 Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: g.screaton{at}imperial.ac.uk (G.S.); j.mongkolsapaya{at}imperial.ac.uk (J.M.)

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