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Sci Rep. 2018 Jan 24;8(1):1474. doi: 10.1038/s41598-018-19874-1.

Vaccine vectors based on Adenovirus 19a/64 exhibit broad cellular tropism and potently restimulate HCMV-specific T cell responses ex vivo.

Author information

1
Institute of Medical Microbiology and Hygiene, Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
2
Institute of Virology, Medical Center - University of Freiburg, Medical Faculty, University of Freiburg, Hermann-Herder Str 11, 79104, Freiburg, Germany.
3
SIRION Biotech GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany.
4
Institute of Medical Microbiology and Hygiene, Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. ralf.wagner@klinik.uni-regensburg.de.
5
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Franz-Josef- Strauß-Allee 11, 93053, Regensburg, Germany. ralf.wagner@klinik.uni-regensburg.de.

Abstract

Human Cytomegalovirus (HCMV) remains a major health burden and the development of a vaccine is a global priority. We developed new viral vectors delivering the T cell immunogens IE-1 and pp65 based on Adenovirus 19a/64 (Ad19a/64), a member of subgroup D. In this ex vivo study, the novel vectors were compared side by side to Ad5 or modified Vaccinia Ankara (MVA) strains expressing the same transgenes. We found that unlike Ad5, Ad19a/64 vectors readily transduce a broad panel of immune cells, including monocytes, T cells, NK cells and monocyte-derived dendritic cells (moDCs). Both Ad19a/64- and MVA-transduced moDCs efficiently restimulated IE-1 or pp65-specific T cells but MVA induced a higher amount of cytotoxicity in this cell type. Ad5 and Ad19 induced upregulation of CD86 and HLA-DR in moDCs whereas expression of CD80 and CD83 was largely unaltered. By contrast, MVA transduction led to downregulation of all markers. Taken together, our data demonstrate that Ad19a/64 is a promising vector for the delivery of HCMV immunogens since it transduces dendritic cells with an efficiency that is comparable to MVA, but cytotoxicity and interference with dendritic cell maturation are less pronounced.

PMID:
29367743
PMCID:
PMC5784015
DOI:
10.1038/s41598-018-19874-1
[Indexed for MEDLINE]
Free PMC Article

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