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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)

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Open Access Green as soon as Postprint is submitted to ZB.

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal Vaccine

Quellenangaben Volume: 35, Issue: 8, Pages: 5131-5139

Publisher Elsevier

Publishing Place Oxford

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Gene Vector (AGV)