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Link, E.K.* ; Brandmüller, C.* ; Suezer, Y.* ; Ameres, S. ; Volz, A.* ; Moosmann, A. ; Sutter, G.* ; Lehmann, M.H.*

A synthetic human cytomegalovirus pp65-IE1 fusion antigen efficiently induces and expands virus specific T cells.

Vaccine 35, 5131-5139 (2017)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA. This recombinant MVA, MVA-syn65_IE1, allowed for the production of a stable ∼120kDa syn65_IE1 fusion protein upon tissue culture infection. MVA-syn65_IE1 infected CD40-activated B cells activated and expanded pp65- and IE1-specific T cells derived from HCMV-seropositive donors to at least equal levels as control recombinant MVA expressing single genes for pp65 or IE1. Additionally, we show that MVA-syn65_IE1 induced HCMV pp65- and IE1-epitope specific T cells in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Thus, MVA-syn65_IE1 represents a promising vaccine candidate against HCMV and constitutes a basis for the generation of a multivalent vaccine targeting relevant pathogens in immunocompromised patients.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Human Herpesvirus-5, Hhv-5 ; Modified Vaccinia Virus Ankara ; Poxvirus ; Vector Vaccine; Recombinant Vaccinia Virus; Allogeneic Bone-marrow; Attenuated Mva Strain; Adoptive Immunotherapy; Host-range; In-vitro; Cellular-immunity; Ie1-pp65 Protein; Influenza-virus; Human Cmv
ISSN (print) / ISBN 0264-410X
e-ISSN 1358-8745
Zeitschrift Vaccine
Quellenangaben Band: 35, Heft: 8, Seiten: 5131-5139 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Oxford
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)