6533b850fe1ef96bd12a83e0

RESEARCH PRODUCT

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

Maja AbramWiebke JägerAdriana TomicStipan JonjićMartin MesserleBojan PolićMaja ArapovićNiels A. W. LemmermannFelix M. WensveenAnnette OxeniusAndreas BuscheMijo GolemacMelanie M. BrinkmannAstrid KrmpotićTihana TršanMarina Babić

subject

Genetic VectorsRetinoic acidCytomegaloviruschemical and pharmacologic phenomenaBiologyCD8-Positive T-LymphocytesEpitopeStatistics Nonparametric03 medical and health scienceschemistry.chemical_compoundMice0302 clinical medicineImmune systemIn vivoCytotoxic T cellAnimalsVector (molecular biology)030304 developmental biologyImmune EvasionMice Knockout0303 health sciencesMice Inbred BALB CVaccines SyntheticMultidisciplinaryBIOMEDICINE AND HEALTHCARE. Basic Medical Sciences.Membrane ProteinsBiological SciencesNKG2DFlow CytometryVirologyListeria monocytogenes3. Good healthCD8 T cell vaccine; RAE-1 gamma; vaccine vectorMice Inbred C57BLchemistryNK Cell Lectin-Like Receptor Subfamily KBIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti.CD8030215 immunology

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.

yearjournalcountryeditionlanguage
2013-09-19Proceedings of the National Academy of Sciences of the United States of America
10.1073/pnas.1310215110https://pubmed.ncbi.nlm.nih.gov/24052528