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Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.

Trsan, Tihana
; 
Busche, Andreas
; 
Abram, Maja
; 
Wensveen, Felix M
; 
Lemmermann, Niels A
; 
Arapovic, Maja
; 
Babic, Marina
; 
Tomic, Adriana
; 
Golemac, Mijo
; 
Brinkmann, Melanie M
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Issue Date
2013-10-08
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Abstract
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.
Citation
Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ. 2013, 110 (41):16550-5 Proc. Natl. Acad. Sci. U.S.A.
Affiliation
Research group viral immune modulation, Helmholtz Centre for infection research, Braunschweig, Germany
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Journal
Proceedings of the National Academy of Sciences of the United States of America
URI
http://hdl.handle.net/10033/311079
DOI
10.1073/pnas.1310215110
PubMed ID
24052528
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Article
Language
en
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1091-6490
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Archived with thanks to Proceedings of the National Academy of Sciences of the United States of America
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publications of the research group viral immunomodulation (VIMM)
publications of the junior research group immunomodulation (VIMM)