We are working at the interface of immunology and virology by studying the unique immunobiology of cytomegalovirus. Using CMV as a vaccine platform we discovered that CMV can be genetically modified to elicit “killer” cells (i.e. CD8-positive, cytotoxic T cells) to other infectious diseases and cancer that display a very unconventional way of recognizing and eliminating target cells. Instead of targeting foreign antigens presented by highly diverse major histocompatibility complex (MHC) molecules, CMV-induced T cells target highly conserved MHC-E molecules. Moreover, such MHC-E-restricted CD8+ T cells eliminate simian immunodeficiency virus (SIV) in non-human primates that were vaccinated with CMV carrying SIV antigens. A central aspect of our research is therefore to figure out how CMV induces this unique immune response (no other vaccine can do this) and why these T cells are superior to “normal” T cells in eliminating SIV. We also want to understand how this can be translated into new vaccines for the human population.

A second aspect of our work is to study the pathology of CMV. Since CMV is the most frequent infectious cause of congenital defects we need to make sure that CMV-based vaccines are safe. Using NHP models we are studying how CMV infects the fetus, what can be done to prevent such infections and how can we design vaccine vectors that can no longer cause disease in immune-deficient hosts while maintaining these unique immunological capabilities.