Dendritic cell-specific antigen delivery by coronavirus vaccine vectors induces long-lasting protective antiviral and antitumor immunity.
Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity.
Cervantes-Barragan
Luisa
L
Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
Züst
Roland
R
Maier
Reinhard
R
Sierro
Sophie
S
Janda
Jozef
J
Levy
Frederic
F
Speiser
Daniel
D
Romero
Pedro
P
Rohrlich
Pierre-Simon
PS
Ludewig
Burkhard
B
Thiel
Volker
V
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D017934:Coronavirus / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D013045:Species Specificity; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control*
D000941:Antigens; D019496:Cancer Vaccines; D014765:Viral Vaccines