Degradome analysis of vaccines
The objective is to develop in vitro antigen degradation assays in order to mimic the fate of the antigen in vivo.
Proteolytic degradation kinetics could be an important indicator for antigen quality and even for immunogenicity (e.g. Egger et al Plos One 2011, Delamarre et al JEM 2006, Watts BBA 2012). Once an antigen is taken up by antigen presenting cells, it will encounter lysosomal and proteasomal proteolytic activity. Some of the resulting peptides act as T-cell epitopes and are presented by MHC molecules to T-cells. Antigen quality, which depends on protein folding, posttranslational modifications, aggregation, covalent changes due to chemical inactivation, affect the susceptibility of the antigen for proteolysis and hence the immunogenicity. The project aims to identify critical parameters of intracellular antigen degradation and, based on this, to develop in vitro assays for quality control of vaccines.