title: Efficient transduction of human monocyte-derived dendritic cells by chimpanzee-derived adenoviral vector.
abstract: Using recombinant adenoviruses (Ads) to target host dendritic cells (DCs) presents an attractive prospect for immunization. The efficacy of commonly used human Ad-derived gene transfer vectors for antigen delivery in humans is often compromised by preexisting anti-Ad immunity, acquired by the majority of human population as a result of frequent naturally occurring virus infections. As an alternative vector we propose chimpanzee-derived recombinant adenoviruses, which are poorly neutralized by human sera. In the present study we examine the ability of one such vector, AdC68, to transduce and activate human monocyte-derived DCs in culture. We found that AdC68 could efficiently transduce both immature and mature DCs at levels similar to those by the human serotype 5 Ad recombinant. Exposure of immature DCs to AdC68 did not alter the expression of activation and maturation marker molecules on the cell surface. Nevertheless, the transduction induced DCs to secrete interferon alpha and interleukin (IL)-6, but not IL-12 or tumor necrosis factor alpha. In addition, AdC68-transduced immature DCs could stimulate proliferation of autologous T lymphocytes. This is the first report describing a chimpanzee-derived recombinant Ad as a vector for transduction of human DCs.
authors.affiliation: Department of Medicine, Medical Genetics Division, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Varnavski
authors.forename: Katia
authors.initials: K
authors.lastname: Schlienger
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bergelson
authors.forename: Guang-Ping
authors.initials: GP
authors.lastname: Gao
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000261:Adenoviruses, Simian / Q000235:genetics*; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000235:genetics; D009000:Monocytes / Q000276:immunology; D002679:Pan troglodytes; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic
chemical_list: D015703:Antigens, CD; D039564:Integrin alphaV; D016898:Interferon-alpha; D015850:Interleukin-6; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins