The invention provides designer nucleic acid constructs and polypeptides that can be used as therapeutic vaccines against HPV 16. These polypeptides comprise essentially all possible T-cell epitopes of HPV 16 oncoproteins E6 and E7, but nevertheless have a strongly reduced (as compared to wt E6 and E7), up to non-detectable, transforming activity, by comprising fragments of the E6 and E7 proteins that have been re-ordered, while at the same time containing a minimized number of undesired neo-epitopes. The invention provides a nucleic acid molecule encoding a polypeptide comprising a sequence as set forth in SEQ ID NO: 1. In certain embodiments, the encoded polypeptide further comprises at least one epitope of a human papillomavirus (HPV) E2 protein, for example an HPV 16 E2 protein.
