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 costi...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2013-10, Vol.110 (41), p.16550-16555
Hauptverfasser: Tršan, Tihana, Busche, Andreas, Abram, Maja, Wensveen, Felix M., Lemmermann, Niels A., Arapović, Maja, Babić, Marina, Tomić, Adriana, Golemac, Mijo, Brinkmann, Melanie M., Jäger, Wiebke, Oxenius, Annette, Polić, Bojan, Krmpotić, Astrid, Messerle, Martin, Jonjić, Stipan
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container_end_page 16555
container_issue 41
container_start_page 16550
container_title Proceedings of the National Academy of Sciences - PNAS
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creator Tršan, Tihana
Busche, Andreas
Abram, Maja
Wensveen, Felix M.
Lemmermann, Niels A.
Arapović, Maja
Babić, Marina
Tomić, Adriana
Golemac, Mijo
Brinkmann, Melanie M.
Jäger, Wiebke
Oxenius, Annette
Polić, Bojan
Krmpotić, Astrid
Messerle, Martin
Jonjić, Stipan
description 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.
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subjects Animals
Biological Sciences
CD8-positive T-lymphocytes
CD8-Positive T-Lymphocytes - immunology
Cross priming
Cytomegalovirus
Cytomegalovirus - genetics
Cytomegalovirus - immunology
Epitopes
Flow Cytometry
Genetic Vectors - genetics
Genetic Vectors - immunology
Immune Evasion - immunology
Infections
Listeria monocytogenes
Listeria monocytogenes - immunology
listeriosis
longevity
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Murid betaherpesvirus 1
Murine cytomegalovirus
neoplasms
NK Cell Lectin-Like Receptor Subfamily K - genetics
Receptors
retinoic acid
Spleen
Statistics, Nonparametric
T lymphocytes
Vaccination
vaccines
Vaccines, Synthetic - immunology
Viruses
title Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ
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