Assessment of a cellular vaccination approach consisting of crawling dendritic cells (CDCs) transduced with HSV-1-Deltapac vectors.
Crawling dendritic cells (CDCs) and herpes simplex virus-1 (HSV-1) amplicon vectors were utilized in this study: (1) to evaluate whether CDCs can be transduced by HSV-1 amplicon vectors; (2) to assess the effects of HSV-1 infections on structure and functions of CDCs; (3) to assess the capabilities of the transduced CDC to express, process, and present the transgene products; and (4) to induce in vitro and in vivo priming of T cells and B cells. CDC supported amplicon-mediated transgene expression while retaining the ability to perform mixed lymphocyte reaction (MLR) and priming of naive T cells. Then it was tested whether transduced CDC were able to initiate immunity against either the amplicon particle and/or the product encoded by the delivered transgene by injecting groups of mice with transduced CDCs expressing GFP or LacZ. Spleen cells of these mice were stimulated by co-incubation with cells expressing: (1) either one of the transgenes (GFP or LacZ), (2) peptides of beta-gal, or (3) peptides of HSV-1 glycoprotein B (gB). Interestingly, no significant cytotoxic T lymphocyte (CTL) activity against the transgenes or against gB was observed. In contrast, mice developed high levels of antibodies against gB and LacZ.Mainly, the findings that CDCs not only express amplicon-delivered transgene, but were able to induce MLR and priming of naïve T cells against the transduced antigen, open up unexpected possibilities and the likelihood to use CDCs as a vehicle for cellular immunization against any transduced antigens. However, these results indicate that HSV-1 amplicon-transduced CDCs induce effective priming and a humoral response, but no strong cell-mediated immune response.
Nuñez
Rafael
R
Institute for Virology, Faculty of Veterinary Medicine, Univ of Zürich, Switzerland. rafaelnr.@uic.edu
Fraefel
Cornel
C
Suter
Mark
M
Nuñez-Liman
Anne
A
Liou
Hsiou-Chi
HC
Ackerman
Mathias
M
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D007156:Immunologic Memory; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes; D014611:Vaccination / Q000379:methods*
D000956:Antigens, Viral; D016207:Cytokines; D049452:Green Fluorescent Proteins