title: Activation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand.
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.
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Tomić
authors.affiliation: Clinics of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Pavankumar R
authors.initials: PR
authors.lastname: Varanasi
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Mijo
authors.initials: M
authors.lastname: Golemac
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Malić
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Riese
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Borst
authors.affiliation: Clinics of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.|German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.
authors.forename: Eva
authors.identifier: http://orcid.org/0000-0002-5678-3775
authors.initials: E
authors.lastname: Mischak-Weissinger
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzmán
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Astrid
authors.initials: A
authors.lastname: Krmpotić
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjić
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.|German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.
authors.forename: Martin
authors.identifier: http://orcid.org/0000-0002-1227-3933
authors.initials: M
authors.lastname: Messerle
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D022482:Cytomegalovirus Vaccines; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C423230:ULBP2 protein, human; D014613:Vaccines, Attenuated