Receptor-mediated targeting of spray-dried lipid particles coformulated with immunoglobulin and loaded with a prototype vaccine.
OBJECTIVE
Spray-dried lipid-based microparticles (SDLM) serve as a platform for delivery of a wide variety of compounds including peptides, proteins, and vaccines to the respiratory mucosa. In the present study, we assessed the impact of IgG-mediated targeting to phagocytic cells of inactivated influenza 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 presenting cells (APC) and a T cell hybridoma (TcH) line specific for a dominant influenza 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 Fc receptor (FcR)-dependent manner by phagocytic APC that were then able to effectively present a dominant, class II-restricted epitope to specific T cells. While SDLM-WSN elicited 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 by 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-mediated targeting to phagocytes.
Bot
A I
AI
Department of Biological Research, Alliance Pharmaceutical Corp, San Diego, California 92121, USA. axb@allp.com
Smith
D J
DJ
Bot
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Dellamary
L
L
Tarara
T E
TE
Harders
S
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Phillips
W
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Weers
J G
JG
Woods
C M
CM
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002214:Capsules / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000378:metabolism; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000008:administration & dosage* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
D000336:Aerosols; D000914:Antibodies, Viral; D002214:Capsules; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008055:Lipids; D011208:Powders; D011961:Receptors, Fc; D015164:Vaccines, Inactivated