title: Optimized recombinant dense bodies of human cytomegalovirus efficiently prime virus specific lymphocytes and neutralizing antibodies without the addition of adjuvant.
abstract: Control of human cytomegalovirus (HCMV) infection correlates with the reconstitution of antiviral T lymphocytes in haematopoietic stem cell transplant recipients. A vaccine to foster this reconstitution and to ameliorate the severe consequences of HCMV reactivation is yet unavailable. This work focused on providing a rationale for the amendment of the yields and the antigenic composition of a vaccine, based on subviral dense bodies (DB) of HCMV. Modified DB were generated that contained the HLA-A2 presented IE1 model peptide TMYGGISLL, integrated at different positions in the major DB protein pp65. Insertion at position W175 of pp65 allowed efficient formation of recDB in the cytoplasm of infected cells and resulted in considerable yields of these particles. Even in the absence of adjuvant, these particles proved to be highly immunogenic with respect to CD8 and CD4 T cell and neutralizing antibody responses.
authors.affiliation: Institute for Virology, University Medical Centre, Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, D-55101 Mainz, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Becke
authors.forename: Steffi
authors.initials: S
authors.lastname: Aue
authors.forename: Doris
authors.initials: D
authors.lastname: Thomas
authors.forename: Sina
authors.initials: S
authors.lastname: Schader
authors.forename: Jürgen
authors.initials: J
authors.lastname: Podlech
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.forename: Tina
authors.initials: T
authors.lastname: Sedmak
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: Bodo
authors.initials: B
authors.lastname: Plachter
authors.forename: Sabine
authors.initials: S
authors.lastname: Reyda
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D022482:Cytomegalovirus Vaccines; D004279:DNA, Viral; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa