The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. A significant need remains however for improved or novel vaccines, particularly for major infectious diseases such as HIV, malaria and tuberculosis, and also for cancer therapeutics.
A key requirement for vaccine efficacy is T lymphocyte activation. Protein-based vaccines are taken up by antigen presenting cells (APCs), broken down into peptides by proteases, and then displayed on MHC molecules on the surface of the APC. Researchers have now shown that too much proteolytic processing within APC can compromise antigen/vaccine presentation to T cells.
Researchers at the University of Dundee have used the novel strategy of suppressing proteolytic activity to significantly enhance T cell responses. Modulation of proteolysis is obtained by a novel multifunctional protease inhibitor termed Cystatin-Pepstatin Inhibitor (CPI).
The novel multifunctional endo/lysosomal protease inhibitor inhibits all three families of the endosomal proteases in an endosome-specific manner. This strategy has the potential to provide a novel, highly effective method of improving vaccine performance and work is ongoing to test CPI as an additive to vaccine adjuvants.