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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cicin-Sain, Luka Jarvis, Michael A. Dekhtiarenko, Iryna Ruzsics, Zsolt |
| Description | Country affiliation: Germany Author Affiliation: Dekhtiarenko I ( Department of Vaccinology, Helmholtz Center for Infection Research, Braunschweig 38124, Germany.) |
| Abstract | Natural immunity to CMV dominates the CD4 and CD8 memory compartments of the CMV-seropositive host. This property has been recently exploited for experimental CMV-based vaccine vector strategies, and it has shown promise in animal models of AIDS and Ebola disease. Although it is generally agreed that CMV-based vaccine vectors may induce highly protective and persistent memory T cells, the influence of the gene expression context on Ag-specific T cell memory responses and immune protection induced by CMV vectors is not known. Using murine CMV (MCMV) recombinants expressing a single CD8 T cell epitope from HSV-1 fused to different MCMV genes, we show that magnitude and kinetics of T cell responses induced by CMV are dependent on the gene expression of CMV Ags. Interestingly, the kinetics of the immune response to the HSV-1 epitope was paralleled by a reciprocal depression of immune responses to endogenous MCMV Ags. Infection with a recombinant MCMV inducing a vigorous initial immune response to the recombinant peptide resulted in a depressed early response to endogenous MCMV Ag. Another recombinant virus, which induced a slowly developing 'inflationary' T cell response to the HSV-1 peptide, induced weaker long-term responses to endogenous CMV Ags. Importantly, both mutants were able to protect mice from a challenge with HSV-1, mediating strong sterilizing immunity. Our data suggest that the context of gene expression markedly influences the T cell immunodominance hierarchy of CMV Ags, but the immune protection against HSV-1 does not require inflationary CD8 responses against the recombinant CMV-expressed epitope. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| Journal | The Journal of Immunology |
| Issue Number | 7 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, Viral Genetics Immunology Gene Expression Immunodominant Epitopes Muromegalovirus Animals Chemistry Cd8-positive T-lymphocytes Disease Models, Animal Epitopes, T-lymphocyte Gene Order Genome, Viral Herpes Simplex Prevention & Control Herpesvirus 1, Human Mice Mutation Peptides Phenotype Virus Replication Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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