Title
Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: Efficient human cell infection and bypass of preexisting adenovirus immunity
Author
Vogels, R.
Zuijdgeest, D.
van Rijnsoever, R.
Hartkoorn, E.
Damen, I.
de Béthune, M.-P.
Kostense, S.
Penders, G.
Helmus, N.
Koudstaal, W.
Cecchini, M.
Wetterwald, A.
Sprangers, M.
Lemckert, A.
Ophorst, O.
Koel, B.
van Meerendonk, M.
Quax, P.
Panitti, L.
Grimbergen, J.
Bout, A.
Goudsmit, J.
Havenga, M.
Publication year
2003
Abstract
Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the identification of human Ad35 as a virus with low global prevalence and the generation of an Ad35 vector plasmid system for easy insertion of heterologous genes. In addition, we have identified the minimal sequence of the Ad35-E1B region (molecular weight, 55,000 [55K]), pivotal for complementation of fully E1-lacking Ad35 vector on PER.C6 cells. After stable insertion of the 55K sequence into PER.C6 cells a cell line was obtained (PER.C6/55K) that efficiently transcomplements both Ad5 and Ad35 vectors. We further demonstrate that transduction with Ad35 is not hampered by preexisting Ad5 immunity and that Ad35 efficiently infects dendritic cells, smooth muscle cells, and synoviocytes, in contrast to Ad5. Chemicals/CAS: Adenovirus E1B Proteins; Antibodies, Viral
Subject
Biology
Biomedical Research
Adenovirus vector
Animal cell
Controlled study
Dendritic cell
Gene insertion
Gene sequence
Gene therapy
Gene transfer
Genetic complementation
Genetic transduction
Human
Human adenovirus
Human adenovirus 35
Human adenovirus 5
Human cell
Immune response
Mouse
Nonhuman
Plasmid
Prevalence
Smooth muscle fiber
Synoviocyte
Vaccination
Virus immunity
Virus replication
Adenovirus E1B Proteins
Adenoviruses, Human
Animals
Antibodies, Viral
Cell Line
Cells, Cultured
Dendritic Cells
Gene Transfer Techniques
Genetic Vectors
Humans
Mice
Mice, Inbred BALB C
Muscle, Smooth
Neutralization Tests
Plasmids
Synovial Membrane
Vaccination
Virus Assembly
Virus Replication
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DOI
https://doi.org/10.1128/jvi.77.15.8263-8271.2003
TNO identifier
237213
ISSN
0022-538X
Source
Journal of Virology, 77 (15), 8263-8271
Document type
article