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1 August 2005

Volume 192, Number 3
The Journal of Infectious Diseases 2005;192:510–519
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19203-0021$15.00
DOI: 10.1086/431520
MAJOR ARTICLE

Dengue Virus (DV) Enhancing Antibody Activity in Preillness Plasma Does Not Predict Subsequent Disease Severity or Viremia in Secondary DV Infection

Kamolwish Laoprasopwattana,1,7

Daniel H. Libraty,1

Timothy P. Endy,3

Ananda Nisalak,6

Supamit Chunsuttiwat,5

David W. Vaughn,4

George Reed,2

Francis A. Ennis,1

Alan L. Rothman,1 and

Sharone Green1

1Center for Infectious Disease and Vaccine Research and 2Department of Medicine, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester; 3Department of Virus Diseases, Walter Reed Army Institute of Research, Washington, DC; 4US Army Medical Research and Materiel Command, Fort Detrick, Maryland; 5Division of General Communicable Diseases, Department of Communicable Disease Control, Ministry of Public Health, and 6Department of Virology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, and 7Pediatric Department, Songklanagarind Hospital, Songkhla, Thailand

Background.Dengue hemorrhagic fever, the most severe form of dengue illness, is associated with secondary dengue virus (DV) infection. Preexisting nonneutralizing antibodies to DV that enhance the infection of Fcγ receptor–bearing cells have been implicated in DV pathogenesis.

Methods.We conducted a prospective cohort study in Thai schoolchildren. Enhancing activity (EA) was measured as the percentage of DV‐infected K562 cells, and viral titer (infected K562 cell supernatants) was measured in preillness plasma samples from children who subsequently had secondary DV2 or DV3 infection.

Results.Plaque‐reduction neutralizing titers to the child’s own DV2 or DV3 isolate were detected in 23 of 32 and 8 of 27 of the preillness plasma samples, and EA was detected to a low‐passage Thai DV2 or DV3 in 31 of 32 and 26 of 27, respectively, of the samples. EA in undiluted preillness plasma did not correlate with subsequent disease severity or peak viremia levels in either secondary DV2 or DV3 infections.

Conclusions.Preillness plasma enhances DV infection of K562 cells even in the presence of detectable neutralizing antibodies in LLC‐MK2 cells. However, levels of preillness plasma EA of DV infection in K562 cells did not correlate with the clinical severity or viral burden of secondary DV infection.

Received 3 December 2004; accepted 26 February 2005; electronically published 5 July 2005.

Reprints or correspondence: Dr. Sharone Green, Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Ave. N., Rm. S5‐326, Worcester, MA 01655 ().

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A. P. Goncalvez, R. E. Engle, M. St. Claire, R. H. Purcell, C.-J. Lai. (2007) Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proceedings of the National Academy of Sciences 104:22, 9422-9427
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Kamolwish Laoprasopwattana, Daniel H. Libraty, Timothy P. Endy, Ananda Nisalak, Supamit Chunsuttiwat, Francis A. Ennis, Alan L. Rothman, and Sharone Green. (2007) Antibody-Dependent Cellular Cytotoxicity Mediated by Plasma Obtained before Secondary Dengue Virus Infections: Potential Involvement in Early Control of Viral Replication. The Journal of Infectious Diseases 195:8, 1108-1116
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Sharone Green, Alan Rothman. (2006) Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Current Opinion in Infectious Diseases 19:5, 429???436
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Donald S. Burke and Srisakul Kliks. (2006) Antibody-Dependent Enhancement in Dengue Virus Infections. The Journal of Infectious Diseases 193:4, 601-603
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Scott B. Halstead. (2006) Measuring Dengue Enhancing Antibodies: Caveats. The Journal of Infectious Diseases 193:4, 601-601
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Sharone Green, Daniel H. Libraty, Kamolwish Laoprasopwattana, Francis A. Ennis, and Alan L. Rothman. (2006) Reply to Halstead and to Burke and Kliks. The Journal of Infectious Diseases 193:4, 603-604
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  • Presented in part: 52nd Annual Meeting of the American Society of Tropical Medicine and Hygiene, Philadelphia, PA, 3–7 December 2003 (abstract 2057); 7th International Symposium on Positive Strand RNA Viruses, San Francisco, CA, 27 May–1 June 2004 (abstract 286).

    Financial support: National Institutes of Health (grant P01‐AI‐34533); US Army Medical Research and Materiel Command.

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