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Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

van der Most, Robbert G. and Murali-Krishna, Kaja and Ahmed, Rafi and Strauss, James H. (2000) Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response. Journal of Virology, 74 (17). pp. 8094-9101. ISSN 0022-538X. PMCID PMC112342.

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We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response.

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Additional Information:Copyright © 2000, American Society for Microbiology. Received 16 February 2000/Accepted 30 May 2000 We thank Charles M. Rice for providing the YFV-17D plasmids, Kenneth H. Eckels for providing the DEN-2 NGC virus, J. Robert Putnak for providing the reagents for neutralizing plaque assays, and Ching-Juh Lai and Margo Brinton for providing the prM- and E- and NS3-expressing vaccinia virus recombinants, respectively. We also thank Thomas P. Monath, Stephen A. Stohlman, Conni C. Bergmann, Jeroen Corver, and Laurie E. Harrington for stimulating discussions and Edith Lenches for technical assistance. This work was supported by NIH grants AI20612 to J.H.S. and R21AI44724 to R.A. ADDENDUM IN PROOF -- Recently, Guirakhoo and coworkers published an article (F. Guirakhoo, R. Weltzin, T. J. Chambers, Z.-X. Zhang, K. Soike, M. Ratterree, J. Arroyo, K. Georgakopoulos, J. Catalan, and T. P. Monath, J. Virol. 74:5477-5485, 2000) that showed that a chimeric YF/DEN-2 virus is immunogenic and provides protective immunity in nonhuman primates. We believe that their data complement our results and that the combined data emphasize the potential of chimeric YF/DEN viruses as vaccine candidates.
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NIHAI 20612
Issue or Number:17
PubMed Central ID:PMC112342
Record Number:CaltechAUTHORS:MOSjvir00
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2196
Deposited By: Archive Administrator
Deposited On:14 Mar 2006
Last Modified:02 Oct 2019 22:51

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