Biodegradable lamellar particles of poly(lactide) induce sustained immune responses to a single dose of adsorbed protein.
The adjuvanticity of lamellar particles of poly(L-lactide) (PLA) towards adsorbed ovalbumin (OVA) was investigated. The aim of vaccine formulation was to maximise the amount of antigen retained on the particles and the time of retention during incubation of the formulations in PBS at 37 degrees C. Unmodified PLA lamellae were capable of adsorbing large quantities of OVA (up to 12.5% w/w) but major and rapid desorption occurred in PBS at 37 degrees C (80% released in 24 h). Retention of OVA on PLA lamellae was improved (25% released in 24 h) by precipitating the particles using aqueous sodium deoxycholate solution (DOC-modified PLA lamellae and lyophilising the lamellae-protein preparation after adsorption. Sustained immune responses were elicited in mice to a single sub-cutaneous injection of OVA adsorbed onto DOC-modified PLA lamellae. The level of antibodies induced and the pattern of response was similar to that induced by an alum-adsorbed OVA formulation. Normally boosting is required to obtain high levels of antibody when OVA is adsorbed on poly(DL-lactide co-glycolide) (PLG) microspheres. The lamellar forms of PLA may function as an efficient immunomodulator by effectively retaining adsorbed antigen and by activating immune cells due to their irregular shape. PLA lamellae have potential to stimulate enhanced immune responses to a variety of adsorbed antigens.
School of Pharmaceutical Sciences, University of Nottingham, University Park, UK.
A G
AG
Coombes
E C
EC
Lavelle
S S
SS
Davis
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000327:Adsorption / Q000187:drug effects; D000818:Animals; D001673:Biodegradation, Environmental; D003840:Deoxycholic Acid / Q000378:metabolism / Q000494:pharmacology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D010047:Ovalbumin / Q000493:pharmacokinetics / Q000494:pharmacology; D011091:Polyesters / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D011091:Polyesters; D011506:Proteins; D003840:Deoxycholic Acid; C033616:poly(lactide); D010047:Ovalbumin