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Activation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand

Authors :
Tomić, Adriana
Varanasi, Pavankumar R.
Golemac, Mijo
Malić, Suzana
Riese, Peggy
Mischak-Weissinger, Eva
Guzman, CA
Krmpotić, Astrid
Jonjić, Stipan
Messerle, Martin
Source :
PLoS Pathogens, Volume 12, Issue 12, ournals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006015
Publication Year :
2016

Abstract

Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells. Infection with the ULBP2-expressing HCMV strain caused diminished cell surface levels of MHC class I molecules. While expression of the NKG2D ligand increased the cytolytic activity of NK cells, NKG2D engagement in CD8+ T cells provided co-stimulation and compensated for lower MHC class I expression. Altogether, our data indicate that triggering of both arms of the immune system is a promising approach applicable to the generation of a live attenuated HCMV vaccine.

Details

Language :
English
ISSN :
15537366 and 15537374
Database :
OpenAIRE
Journal :
PLoS Pathogens, Volume 12, Issue 12, ournals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006015
Accession number :
edsair.dedup.wf.001..a767dbb83e559997bff0d60b01e26adc