Enhancement of capsid gene expression: Preparing the human papillomavirus type 16 major structural gene L1 for DNA vaccination purposes

Expression of the structural proteins L1 and L2 of the human papillomavirus es (HPV) is tightly regulated. As a consequence, attempts to express these prime-candidate genes for prophylactic vaccination against papillomavirus-a ssociated diseases in mammalian cells by means of simple DNA transfections result in insufficient production of the viral antigens. Similarly, in vivo DNA vaccination using HPV L1 or L2 expression constructs produces only wea k immune responses. In this study we demonstrate that transient expression of the HPV type 16 L1 and L2 proteins can be highly improved by changing th e RNA coding sequence, resulting in the accumulation of significant amounts of virus-like particles in the nuclei of transfected cells. Data presented indicate that, in the case of L1, adaptation for codon usage accounts for the vast majority of the improvement in protein expression, whereas transla tion-independent posttranscriptional events contribute only to a minor degr ee. Finally, the adapted L1 genes demonstrate strongly increased immunogeni city in vivo compared to that of unmodified L1 genes.