Biodegradable microparticles for the mucosal delivery of antibacterial and dietary antigens.
Mucosal administration of antigen is known to be appropriate for vaccine purposes as well as tolerance induction. Biodegradable poly(DL-lactide-co-glycolide) (PLGA) microparticles were used to deliver both antibacterial phosphorylcholine (PC) and dietary antigen beta lactoglobulin (BLG) by mucosal route. In a first study, the protective immunity elicited by intragastric vaccination with PC encapsulated in microparticles was evaluated in a mouse model against intestinal infection by Salmonella typhimurium and pulmonary infection by Streptococcus pneumoniae. A significant rise in anti-PC immunoglobulin A (IgA) titers, as measured by an enzyme-linked immunosorbent assay, was observed in the intestinal secretions after oral immunization with PC-loaded microparticles compared with the titers of mice immunized with free PC-thyr or blank microparticles. This antibody response correlated with a highly significant resistance to oral challenge by S. typhimurium. IgA in pulmonary secretion were not able to protect against S. pneumoniae infection. BALB/c mice were, therefore, immunized intranasally (i.n.). Immunization was followed by a rise in anti-PC IgA and IgG titers in serum and in pulmonary secretions by both free and encapsulated PC-Thyr. The survival rates were 91 and 76% in the two groups of mice, respectively. In a second study and in order to prevent allergy against milk by inducing oral tolerance, one of the major allergenic milk protein, BLG was entrapped into microparticles. Oral administration of microparticles containing BLG reduced significantly (by 10000) the amount of protein necessary to decrease both specific anti BLG IgE and DTH response. These studies demonstrate the ability of microparticles to induce both mucosal immunity and oral tolerance.
Fattal
Elias
E
School of Pharmacy, University of Paris Sud, UMR CNRS 8612, 5 rue Jean-Baptiste Clement, Châtenay-Malabry, France. elias.fattal@cep.u-psud.fr
Pecquet
Sophie
S
Couvreur
Patrick
P
Andremont
Antoine
A
D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000941:Antigens / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D005079:Excipients; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology*; D007136:Immunoglobulins / Q000032:analysis / Q000096:biosynthesis; D019344:Lactic Acid; D007782:Lactoglobulins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010316:Particle Size; D011008:Pneumococcal Infections / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012480:Salmonella Infections / Q000276:immunology / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000941:Antigens; D005079:Excipients; D007136:Immunoglobulins; D007782:Lactoglobulins; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid