title: Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of preexisting adenovirus immunity.
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.
authors.affiliation: Vaccine R&D Division, Crucell Holland BV, 2301CA Leiden, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Vogels
authors.forename: David
authors.initials: D
authors.lastname: Zuijdgeest
authors.forename: Richard
authors.initials: R
authors.lastname: van Rijnsoever
authors.forename: Eric
authors.initials: E
authors.lastname: Hartkoorn
authors.forename: Irma
authors.initials: I
authors.lastname: Damen
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: de Béthune
authors.forename: Stefan
authors.initials: S
authors.lastname: Kostense
authors.forename: Germaine
authors.initials: G
authors.lastname: Penders
authors.forename: Niels
authors.initials: N
authors.lastname: Helmus
authors.forename: Wouter
authors.initials: W
authors.lastname: Koudstaal
authors.forename: Marco
authors.initials: M
authors.lastname: Cecchini
authors.forename: Antoinette
authors.initials: A
authors.lastname: Wetterwald
authors.forename: Mieke
authors.initials: M
authors.lastname: Sprangers
authors.forename: Angelique
authors.initials: A
authors.lastname: Lemckert
authors.forename: Olga
authors.initials: O
authors.lastname: Ophorst
authors.forename: Björn
authors.initials: B
authors.lastname: Koel
authors.forename: Michelle
authors.initials: M
authors.lastname: van Meerendonk
authors.forename: Paul
authors.initials: P
authors.lastname: Quax
authors.forename: Laura
authors.initials: L
authors.lastname: Panitti
authors.forename: Jos
authors.initials: J
authors.lastname: Grimbergen
authors.forename: Abraham
authors.initials: A
authors.lastname: Bout
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Menzo
authors.initials: M
authors.lastname: Havenga
mesh_terms: D017501:Adenovirus E1B Proteins / Q000737:chemistry / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000166:cytology / Q000821:virology; D009500:Neutralization Tests; D010957:Plasmids; D013583:Synovial Membrane / Q000166:cytology / Q000821:virology; D014611:Vaccination; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D017501:Adenovirus E1B Proteins; D000914:Antibodies, Viral