Assessment of a cellular vaccination approach consisting of crawling dendritic cells (CDCs) transduced with HSV-1-†pac vectors

Authors: Nuñez, Rafael¹; Fraefel, Cornel²; Suter, Mark²; Nuñez-Liman, Anne³; Liou, Hisou-Chi⁴; Ackerman, Mathias²

Source: Immunologic Research, Volume 30, Number 1, August 2004 , pp. 105-124(20)

Buy & download fulltext article:

Price: $42.00 plus tax (Refund Policy)

Abstract:

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 ggainst 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 β-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.

Keywords: Dendritic cells; Amplicon-HSV-1; Transduction; Infection; Cellular vaccine; CDC priming

Document Type: Research article

DOI: http://dx.doi.org/10.1385/IR:30:1:105

Affiliations: 1: Institute for Virology, Faculty of Veterinary Medicine, University of Zürich, Winterthurerstrasse 266a, 8057, Zürich, Switzerland, Email: rafehr@uic.edu 2: Institute for Virology, Faculty of Veterinary Medicine, University of Zürich, Winterthurerstrasse 266a, 8057, Zürich, Switzerland, 3: LARC, Rockefeller University, New York, NY, 4: Division of Immunology, Weill Medical College of Cornell University, New York, NY,

Publication date: 2004-08-01

Assessment of a cellular vaccination approach consisting of crawling dendritic cells (CDCs) transduced with HSV-1-†pac vectors

Buy & download fulltext article:

Tools

Key

Text size:

Useful pages