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

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...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2016-12, Vol.12 (12), p.e1006015-e1006015
Main Authors: Tomić, Adriana, Varanasi, Pavankumar R, Golemac, Mijo, Malić, Suzana, Riese, Peggy, Borst, Eva M, Mischak-Weissinger, Eva, Guzmán, Carlos A, Krmpotić, Astrid, Jonjić, Stipan, Messerle, Martin
Format: Article
Language:English
Subjects:
Adaptive Immunity - immunology
Animals
Biology and Life Sciences
Cytomegalovirus - immunology
Cytomegalovirus infections
Cytomegalovirus Infections - immunology
Cytomegalovirus Vaccines - immunology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
GPI-Linked Proteins - immunology
Humans
Immune response regulation
Immunity, Innate - immunology
Immunohistochemistry
Intercellular Signaling Peptides and Proteins - immunology
Killer Cells, Natural - immunology
Ligands
Medicine and Health Sciences
Mice
Prevention
Real-Time Polymerase Chain Reaction
Research and Analysis Methods
Testing
Vaccines, Attenuated - immunology
Viral vaccines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006015