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

2.50
Hdl Handle:
http://hdl.handle.net/10033/620686
Title:
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; Borst, Eva M; Mischak-Weissinger, Eva; Guzmán, Carlos A; Krmpotić, Astrid; Jonjić, Stipan; Messerle, Martin
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.
Affiliation:
Hel,holtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Activation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand. 2016, 12 (12):e1006015 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Dec-2016
URI:
http://hdl.handle.net/10033/620686
DOI:
10.1371/journal.ppat.1006015
PubMed ID:
27907183
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorTomić, Adrianaen
dc.contributor.authorVaranasi, Pavankumar Ren
dc.contributor.authorGolemac, Mijoen
dc.contributor.authorMalić, Suzanaen
dc.contributor.authorRiese, Peggyen
dc.contributor.authorBorst, Eva Men
dc.contributor.authorMischak-Weissinger, Evaen
dc.contributor.authorGuzmán, Carlos Aen
dc.contributor.authorKrmpotić, Astriden
dc.contributor.authorJonjić, Stipanen
dc.contributor.authorMesserle, Martinen
dc.date.accessioned2017-01-09T15:08:43Z-
dc.date.available2017-01-09T15:08:43Z-
dc.date.issued2016-12-
dc.identifier.citationActivation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand. 2016, 12 (12):e1006015 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid27907183-
dc.identifier.doi10.1371/journal.ppat.1006015-
dc.identifier.urihttp://hdl.handle.net/10033/620686-
dc.description.abstractDevelopment 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleActivation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand.en
dc.typeArticleen
dc.contributor.departmentHel,holtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPLoS pathogensen

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