1. ¹Department of Virology, Saarland University, Homburg, Germany
2. ²Medical Department IV, Saarland University, Homburg, Germany
3. ³Research Department, Kantonal Hospital St Gallen, St Gallen, Switzerland

Correspondence: Professor A Meyerhans, Department of Virology, Institute of Microbiology and Hygiene, Saarland University, Kirrbergerstr. 47, Homburg 66421, Germany. E-mail: andreas.meyerhans@uniklinikum-saarland.de

⁴Current address: Department of Pediatric Hematology and Oncology, Saarland University, 66421 Homburg, Germany.

Received 14 August 2007; Accepted 20 September 2007; Published online 6 December 2007.

Abstract

Protein-based immunogens are usually poor inducers of CD8⁺ T cells. To enhance the induction of CD8⁺ T cells, one approach is the use of protein immunogens coupled to protein transduction domains (PTDs). These are small cationic peptide sequences that significantly enhance the uptake of fused proteins into dendritic cells (DC) and then mediate their presentation in the context of major histocompatibility complex class I (MHC-I) and MHC-II molecules. One drawback of this system is the high concentrations of PTD-fusion proteins required. Here, we show that proteins fused to the human cytomegalovirus tegument protein pp65 were bound with higher efficiency to DCs than those fused to the described PTDs TatPTD and Penetratin. Furthermore, the fusion of pp65 to proteins led to an enhanced uptake of these proteins by DCs. Once taken up, CD4⁺ and CD8⁺ memory T cells were strongly stimulated ex vivo demonstrating that pp65 was efficiently processed and presented in the context of both MHC-I and MHC-II. These data make pp65 a promising delivery system to induce cellular immune responses by fused protein vaccines.