Prophylactic DNA immunization against multiple papillomavirus types

At least 15 different papillomavirus types are causatively associated with the development of tumors in humans. Since the middle of 2006 a protective, virus-like particle based vaccine against the tumor-related HPV types 16 and 18 is commercially available. We investigated the possibility of applying DNA vaccination to obtain protective antibody responses against multiple papillomavirus types. Our data indicate that low amounts of DNA were sufficient to induce neutralizing antibodies in mice although a DNA dose-dependency in respect to the L1-specific antibody titers was observed. Furthermore, we found that immune responses against different PV types could be induced by simultaneous DNA vaccination with a mixture of expression vectors encoding L1 proteins of different papillomavirus types. However, we observed that there was a strong interference when plasmids encoding different L1 genes were used together. HPV 16 responses were repressed by co-administration of HPV 11 and/or BPV 1 L1 expression constructs. Likewise, BPV 1 responses were repressed by co-administration of HPV 16 or HPV 11 L1 plasmids. This interference could be overcome by administration of the different constructs into different sites of the animals or by sequential immunization. Thus, our results suggest that the mode of repression was due to interference with L1 particle assembly and was not a consequence of immunodominance of certain L1 proteins.