Receptor-mediated targeting of spray-dried lipid particles coformulated with immunoglobulin and loaded with a prototype vaccine

Purpose. Spray-dried lipid-based microparticles (SDLM) serve as a platform for delivery of a wide variety of compounds including peptides, proteins, a nd vaccines to the respiratory mucosa. In the present study, we assessed th e impact of IgC-mediated targeting to phagocytic cells of inactivated influ enza virus formulated in SDLM, on subsequent immune responses. Methods. SDLM were produced containing inactivated influenza virus strain A /WSN/32/H1N1 (WSN), with or without IgG. Using phagocytic antigen presentin g cells (APC) and a T cell hybridoma (TcH) line specific for a dominant inf luenza virus epitope, we compared the in vitro responses elicited by ligand -formulated (SDLM-IgG-WSN) and non-ligand particles (SDLM-WSN). The effect of including the IgG ligand in the formulation was further characterized by measuring the immune responses of rodents vaccinated with SDLM. Results. SDLM-IgG-WSN were internalized in an Pc receptor (FcR)-dependent m anner by phagocytic APC that were then able to effectively present a domina nt, class II-restricted epitope to specific T cells. While SDLM-WSN elicite d a lower response than administration of plain inactivated virus in saline , the level of the T cell response was restored both in vitro and in vivo b y incorporating the APC FcR ligand, IgG, in the SDLM. Conclusions. Incorporation of FcR ligand (IgG) in SDLM restored the limited ability of formulated virus to elicit T-cell immunity, by receptor-mediate d targeting to phagocytes.