I am working on developing vaccines to protect against human pathogens. These efforts segregate into two complementary areas.
The first area is aimed at understanding the biological mechanisms of how adjuvants stimulate the immune system. Much of my activity in this area has focused on the adjuvant effects and adjuvant mechanisms of bacterial flagellin. Flagellin is expressed by gram negative bacteria and is the major structural component of flagella. Flagellin is also the ligand for Toll Like Receptor 5, which is a relatively conserved molecule expressed by mammals, birds, and fishes. Stimulation of TLR5 by flagellin conveys a danger signal to the host and triggers an innate immune response to help limit infection. Several groups have shown that activating this innate response at the time of immunization results in a more effective adaptive immune response to other components in the vaccine. I have shown that direct stimulation of dendritic cells that express TLR5 is a key step in the adjuvant mechanism of flagellin. The end goal of these activities is to better understand how the innate immune response facilitates the formation of effective cellular and humoral immunological memory.
Secondly, I am working to develop novel vaccine platforms. Much of this effort involves flagellin but also encompasses other variables such as the physical form or size of the antigen and physical linkage of the vaccine antigen to the adjuvant. All of these variables have been shown to impact the response to immunization.
