Rational approaches to immune regulation

Abstract

Our studies are mainly focused on developing strategies of immune regulation. In the case of infectious and neoplastic disease, our approach is to upregulate cell-mediated immunity to viral of tumor antigens using an intracellular bacterium as a vector for targeting these antigens to the major histocompatibility complex (MHC) class I and class II pathways of antigen processing, in addition to exploiting the adjuvant properties of the vector to stimulate innate immunity. In the area of autoimmunity, we are attempting to downregulate the immune response by specific immune intervention directed against autoreactive T cells. In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor (TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease.

Use of the α-hemolysin secretion system of Escherichia coli for antigen delivery in the Salmonella typhi Ty21a vaccine strain

“…In order to achieve stable expression of heterologous antigens in attenuated LBV, several different strategies were developed (Tijhaar et al, 1994;Gentschev et al, 1996;Russmann et al, 1998;Xu et al, 1998;Roberts et al, 1998;Paterson, 2003). One of the most promising approaches in this direction is the use of the E. coli ahemolysin (HlyA) secretion system for antigen delivery .…”

Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors

“…We have long believed that the type of immunity induced by the facultative intracellular parasite Listeria monocytogenes could be ideal for boosting the immune response to foreign antigens [2]. It has been shown that L. monocytogenes enters the host cell and is taken up in a phagosome.…”

“…We have shown that recombinant forms of this organism which have been transformed to express foreign antigens are excellent vectors for targeting foreign antigens to the MHC class I pathway of antigen processing with the generation of authentic CTL epitopes. In the past we have successfully used this unusual vector to target viral antigens from influenza, HIV, and SIV and tumor associated antigens [2]. However, vaccine approaches to target tumor antigens have to overcome additional problems to those presented by vaccines against infectious disease.…”