The primary focus of research in my laboratory is in the areas of antigen (Ag) processing/presentation and vaccine development. Ag presentation is a critical component of an effective immune response against most pathogens. The basic tenet of research in my laboratory is that by better understanding Ag processing and presentation, the cell types involved, and mechanisms for enhancing Ag presentation, one can better understand how to develop more effective vaccine strategies.
It has been known since the mid-1980's that Ag bound to antibody (Ab) in the form of soluble Ab-Ag complexes is presented by Fc receptor-bearing Ag presenting cells to Ag-specific T cells approximately 100 fold more efficiently than Ag alone. While current funding in my laboratory is directed at understanding these and other issues related to Fc receptor-dependent enhancement of Ag presentation by mouse and human monocytes, macrophages, and dendritic cells, the ultimate goal of this laboratory is to convert knowledge gained from these studies into clinical application.
Our studies, and those of other laboratories, indicate that targeting Ag to Ag presenting cells can significantly enhance T cell activation in vitro. In 2008, we demonstrated for the first time that targeting immunogen to Fc receptors intranasally via mAb-inactivated Francisella tularensis (iFt) complexes could enhance protection against the highly lethal F. tularensis organism SchuS4 (a category A biothreat agent). Using human Fc gamma receptor type I transgenic mice, we have also shown that targeting Ag to human Fc gamma receptor type I intranasally using an anti-human Fc gamma receptor type I-PspA (Ag) fusion protein can significantly enhance Ab production, cytokine responses, and protection against PspA-expressing Streptococcus pneumoniae. Importantly, use of adjuvant was not required.
Thus, the current focus of the laboratory is on the development of adjuvant-independent vaccines through Fc receptor targeting of protective immunogens at mucosal sites. In particular, as it applies to mouse and human immune responses to F. tularensis, S. pneumoniae (a common respiratory pathogen), and HIV. Ultimately, we expect these studies, and this vaccine strategy, will have wide applicability to vaccines against a variety of pathogens in adult, pediatric, and immunocompromised populations.