Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.
Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
Tihana
T
Trsan
Andreas
A
Busche
Maja
M
Abram
Felix M
FM
Wensveen
Niels A
NA
Lemmermann
Maja
M
Arapovic
Marina
M
Babic
Adriana
A
Tomic
Mijo
M
Golemac
Melanie M
MM
Brinkmann
Wiebke
W
Jäger
Annette
A
Oxenius
Bojan
B
Polic
Astrid
A
Krmpotic
Martin
M
Messerle
Stipan
S
Jonjic
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D057131:Immune Evasion / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics; D018709:Statistics, Nonparametric; D014614:Vaccines, Synthetic / Q000276:immunology*
C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491217:Raet1c protein, mouse; D014614:Vaccines, Synthetic
CD8 T cell vaccine; RAE-1 gamma; vaccine vector