TY - JOUR A1 - Öhlschläger, Peter A1 - Quetting, Michael A1 - Alvarez, Gerardo A1 - Dürst, Matthias A1 - Gissmann, Lutz A1 - Kaufmann, Andreas M. T1 - Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants JF - International Journal of Cancer Y1 - 2009 SN - 1097-0215 VL - 125 IS - 1 SP - 189 EP - 198 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Almajhdi, Fahad N. A1 - Senger, Tilo A1 - Amer, Haitham M. A1 - Gissmann, Lutz A1 - Öhlschläger, Peter T1 - Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling) JF - PLOS one N2 - Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0113461 SN - 1932-6203 VL - 11 IS - 9 PB - PLOS CY - San Francisco ER -