title: Differential effects of viral vectors on migratory afferent lymph dendritic cells in vitro predict enhanced immunogenicity in vivo.
abstract: Targeting dendritic cells (DC) is key to driving effective immune responses. Lymphatic cannulation provides access to the heterogeneous populations of DC draining peripheral sites in rodents and ruminants. Afferent lymph DEC-205(+) CD11c(+) SIRPα(+) DC were preferentially infected ex vivo with three vaccine viral vectors: recombinant human replication-defective human adenovirus 5 (rhuAdV5), recombinant modified vaccinia virus Ankara (rMVA), and recombinant fowlpox virus (rFPV), all expressing green fluorescent protein (GFP). The rhuAdV5-infected cells remained viable, and peak GFP expression was observed 16 to 24 h posttransduction. Increasing the incubation period of DC with rhuAdV5 enhanced GFP expression. In contrast, DC infected with rMVA-GFP or rFPV-GFP became rapidly apoptotic and GFP expression peaked at 6 h postinfection. Delivery of foot-and-mouth disease virus (FMDV) A(22) antigen to DC by rhuAdV5-FMDV-A(22) ex vivo resulted in significantly greater CD4(+) T cell proliferation than did delivery by rFPV-FMDV-A(22). Delivery of rhuAdV5-GFP in oil adjuvant in vivo, to enhance DC-vector contact, resulted in increased GFP expression in migrating DC compared to that with vector alone. Similarly, CD4(+) T cell responses were significantly enhanced when using rhuAdV5-FMDV-A(22) in adjuvant. Therefore, the interaction between viral vectors and afferent lymph DC ex vivo can predict the outcome of in vivo immunization and provide a means of rapidly assessing the effects of vector modification.
authors.affiliation: The Institute for Animal Health, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Cubillos-Zapata
authors.forename: E
authors.initials: E
authors.lastname: Guzman
authors.forename: A
authors.initials: A
authors.lastname: Turner
authors.forename: S C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: H
authors.initials: H
authors.lastname: Prentice
authors.forename: J C
authors.initials: JC
authors.lastname: Hope
authors.forename: B
authors.initials: B
authors.lastname: Charleston
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D049109:Cell Proliferation; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology; D005587:Fowlpox virus / Q000276:immunology* / Q000472:pathogenicity; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000472:pathogenicity; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines