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PMID: 12857895 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of preexisting adenovirus immunity.

Journal of virology ·Vol. 77 ·No. 15 ·2003-08-00 ·Pages 8263-71

Vogels R, Zuijdgeest D, van Rijnsoever R, Hartkoorn E, Damen I, de Béthune MP, 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

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.

MeSH Terms
Adenovirus E1B Proteins/chemistry,genetics Adenoviruses, Human/genetics,immunology,physiology Animals Antibodies, Viral/immunology Cell Line Cells, Cultured Dendritic Cells/virology Gene Transfer Techniques Genetic Vectors/administration & dosage,immunology Humans Mice Mice, Inbred BALB C Muscle, Smooth/cytology,virology Neutralization Tests Plasmids Synovial Membrane/cytology,virology Vaccination Virus Assembly Virus Replication
Chemicals
Adenovirus E1B Proteins Antibodies, Viral
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Vogels Ronald
Vaccine R&D Division, Crucell Holland BV, 2301CA Leiden, The Netherlands.
Zuijdgeest David
van Rijnsoever Richard
Hartkoorn Eric
Damen Irma
de Béthune Marie-Pierre
Kostense Stefan
Penders Germaine
Helmus Niels
Koudstaal Wouter
Cecchini Marco
Wetterwald Antoinette
Sprangers Mieke
Lemckert Angelique
Ophorst Olga
Koel Björn
van Meerendonk Michelle
Quax Paul
Panitti Laura
Grimbergen Jos
Bout Abraham
Goudsmit Jaap
Havenga Menzo
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.15.8263-8271.2003
Published
2003-08-00
Pages
8263-71
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC165227
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.77.15.8263-8271.2003 PMC Full Text View journal details
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