title: Virus-mediated delivery of antigenic epitopes into dendritic cells as a means to induce CTL.
abstract: Dendritic cells (DC) are potent inducers of CD8+ T cells and can stimulate protective antitumor immunity when pulsed with an antigenic peptide or protein. We used a replication-deficient adenovirus containing a Kb-restricted antigenic peptide of chicken OVA to study CTL induction in vitro and in vivo after adenovirus-mediated gene transfer into DC. The efficiency of adenovirus-infected DC in eliciting a specific CTL response was compared with immunizations with a recombinant vaccinia virus and DC pulsed with peptide or protein. An immortalized DC line derived from a C57BL/6 mouse and freshly isolated splenic DC from C57BL/6 mice were used in CTL induction. Virus-infected DC elicited the strongest Ag-specific CTL response in vitro and in vivo and induced protective antitumor immunity to a challenge with EG.7 tumors (EL-4 cell line expressing OVA). Direct immunization of mice with recombinant adenovirus resulted in the induction of high titers of neutralizing Abs, which precluded a boost of a CTL response after repeated inoculations. However, repeated injections of virus-infected DC induced only low titers of neutralizing Abs. Furthermore, the presence of neutralizing Abs specific for the virus did not affect the usefulness of infected DC as repeated applications of virus-infected DC boosted the CTL response even in mice previously infected with the recombinant vector. The use of DC infected with a recombinant virus has advantages over other forms of immunization and could provide an alternative approach for designing vaccination therapies.
authors.affiliation: Department of Immunology, University of Washington, Seattle 98195, USA.
authors.forename: P
authors.initials: P
authors.lastname: Brossart
authors.forename: A W
authors.initials: AW
authors.lastname: Goldrath
authors.forename: E A
authors.initials: EA
authors.lastname: Butz
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: M J
authors.initials: MJ
authors.lastname: Bevan
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000276:immunology*; D007115:Immunization Schedule; D039564:Integrin alphaV; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D000939:Epitopes; D039564:Integrin alphaV; D016023:Integrins