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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2016
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| _version_ | 1826299387393867776 |
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| author | Tomić, A Varanasi, P Golemac, M Malić, S Riese, P Borst, E Mischak-Weissinger, E Guzmán, C Krmpotić, A Jonjić, S Messerle, M |
| author_facet | Tomić, A Varanasi, P Golemac, M Malić, S Riese, P Borst, E Mischak-Weissinger, E Guzmán, C Krmpotić, A Jonjić, S Messerle, M |
| author_sort | Tomić, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:01:11Z |
| format | Journal article |
| id | oxford-uuid:d85505d1-a6d2-4ff6-8de1-e5d3ed6e136e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:01:11Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:d85505d1-a6d2-4ff6-8de1-e5d3ed6e136e2022-03-27T08:47:45ZActivation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligandJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d85505d1-a6d2-4ff6-8de1-e5d3ed6e136eEnglishSymplectic Elements at OxfordPublic Library of Science2016Tomić, AVaranasi, PGolemac, MMalić, SRiese, PBorst, EMischak-Weissinger, EGuzmán, CKrmpotić, AJonjić, SMesserle, MDevelopment 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. |
| spellingShingle | Tomić, A Varanasi, P Golemac, M Malić, S Riese, P Borst, E Mischak-Weissinger, E Guzmán, C Krmpotić, A Jonjić, S Messerle, M Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand |
| title | Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand |
| title_full | Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand |
| title_fullStr | Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand |
| title_full_unstemmed | Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand |
| title_short | Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand |
| title_sort | activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an nkg2d ligand |
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