Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response.
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.
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. rgvande@emory.edu
R G
RG
van Der Most
K
K
Murali-Krishna
R
R
Ahmed
J H
JH
Strauss
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000235:genetics*; D018792:Encephalitis, Viral / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015005:Yellow fever virus / Q000235:genetics*
D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C074932:prM protein, Flavivirus