Anti-tuberculosis host response modulation through immune cell targeting

Abstract

Development of a subunit tuberculosis vaccine based on a peptide from the immunogenic M. tuberculosis protein Ag85B was studied. Dendritic cells (DCs) are antigen-presenting cells that drive T cell responses in tuberculosis. The integrin-binding arginine-glysine-asparate (RGD) motif was included at the N-terminus of the Ag85B peptide for DC targeting. Immunological effects on bone-marrow differentiated DCs were compared between Ag85B and RGD-Ag85B peptides. RGD-Ag85B peptide was taken up more efficiently, processed by both major histocompatibility complex (MHC) class I and II pathways and induced a higher level of interleukin-12 production. In murine immunisation experiments, RGD-Ag85B was introduced subcutaneously, with a Th1-inducing adjuvant, after prior in vivo fms-like tyrosine kinase (Flt3) immunisation to expand the DC population. A relatively higher level of T cell proliferation, interleukin-2 and interferon-N3 production, as well as induction of antigen-specific T cells, was noted compared to unimmunised mice. This strategy may be a useful way of improving subunit vaccine immunogenicity.