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Am. J. Trop. Med. Hyg., 69(6 suppl), 2003, pp. 39-47
Copyright © 2003 by The American Society of Tropical Medicine and Hygiene

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SEROTYPE-SPECIFIC TH1 RESPONSES IN RECIPIENTS OF TWO DOSES OF CANDIDATE LIVE-ATTENUATED DENGUE VIRUS VACCINES

WILLIAM GWINN, WELLINGTON SUN, BRUCE L. INNIS, JEFFREY CAUDILL, AND ALAN D. KING
Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland

As part of a larger vaccine study, peripheral blood mononuclear cells (PBMC) were collected from volunteers for analysis of vaccine- induced T cell responses. The PBMC were re-stimulated in vitro with live dengue virus and assayed for Th1 or Th2 memory cell responses. Re-stimulated PBMC from the volunteers predominantly secreted interferon-{gamma}. Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a Th1 type of T cell response. The interferon-{gamma} response was primarily serotype-specific with some serotype cross-reactivity. T cell depletion studies showed that the interferon-{gamma} was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes. CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes. However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes. In summary, an antigen-specific Th1 type T cell response was seen as a response to vaccination using live attenuated dengue virus.

Acknowledgments: We thank Dr. Robert Putnak for preparation of the viruses used in the stimulation assays, and Dr. Stuart Cohen for preparation of some of the primers used in the study.

Financial support: This study was supported by the United States Army Medical Research and Materiel Command.

Authors’ addresses: William Gwinn, Department of Microbiology and Tropical Medicine, The George Washington University Medical Center, 2300 Eye Street, NW, Washington, DC 20037. Wellington Sun and Jeffrey Caudill, Division of Communicable Diseases and Immunology, Department of Virus Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910. Bruce L Innis, GlaxoSmithKline, 1250 South Collegeville Road, Mail Code UP4330, Collegeville, PA 19426-0989. Alan D. King, Cyto Pulse Sciences, Inc., PO Box 1609, Columbia, MD 21045, Telephone: 410-715-0990. Fax: 410- 715-2148, E-mail: alan{at}cytopulse.com.




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ERRATA
Am J Trop Med Hyg, March 1, 2004; 70(3): 336 - 337.
[Full Text] [PDF]


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Copyright © 2003 by the American Society of Tropical Medicine and Hygiene.