Immune activation induced by papillomavirus-like particles

Erwin Schrödinger Fellowship J 1974 Immune activation induced by papillomavirus-like particles Petra LENZ 09.10.2000 Papillomavirus-like particles (VLPs) are potent inducers of humoral and cellular immune responses, making them attractive candidates for non-infectious subunit vaccines. To investigate the mechanisms underlying VLP-induced immunity we previously focused on the effects of VLP exposure to dendritic cells (DCs) given their essential role in the initiation and modulation of immune responses. We found that VLPs are effectively bound and rapidly internalized by murine bone marrow derived dendritic cells (BNMCs) that subsequently acquired a mature phenotype, secreted proinflammatory cytokines and induced T111-dominated, primary T cell responses. Based on these results, we will further characterize the pathways of antigen processing used for subsequent antigen presentation to investigate how VLP-derived peptides enter the MHC class I- and class 11 pathways. We will also address the question whether DC activation by naked icosahedral virions is a general phenomenon that results from interaction of pattern recognition receptors on the DC surface with the highly rigid ordered virion structure as hypothesized for B cells. In addition, the studies initiated to investigate the adjuvant effect of VLPs on induction of cross-neutralizing antibodies against subdominat L2-epitopes will be continued. The results of our studies will contribute significantly to a better understanding of anti-virion immunity and to the development of VLP-based prophylactic and therapeutic vaccines.