Nate Berkowitz

Intracellular pathogens present a significant challenge for vaccine development as these agents invade host cells and are able to avoid initial recognition by the host immune system. Intracellular pathogens often multiply undetected until cytotoxic T-lymphocytes (CTL) recognize foreign antigenic peptides displayed in association with surface MHC class I molecules and are activated to kill the infected host cell.

I have been working with a modified version of listeriolysin O (LLO) that retains full cytolytic activity but is not secreted. L. monocytogenes expressing this cytoplasmic LLO are unable to escape the vacuole and do not replicate within host cells. However, when these bacteria are eventually degraded within phagosomes, active cytoplasmic LLO is released and perforates the phagosomal membrane. Antigens from the degraded bacteria can then enter the cytosol and be processed for presentation on host cell MHC class I molecules. CTL can then recognize displayed antigenic peptides and generate an immune response.

I am investigating whether cytoplasmic LLO-expressing bacteria can function as a safe and effective vaccine strategy against L. monocytogenes.

View Larger Image