Vaccine properties of antigens entrapped in microparticles produced by spray-drying technique and using various polyester polymers.
The present study investigated the suitability of various microparticles produced by spray-drying technique to entrap and preserve the physiochemical and biological properties of an antigen. These microparticles were constituted either by poly(lactide) polymers characterized by various molecular weight or poly(lactide-co-glycolide) polymers. The recombinant 28 kDa glutathione S-transferase of Schistosoma mansoni (rSm28GST) characterized by major epitopes involved in the active site of this enzyme was selected as model antigen. The microparticles were characterized by a mean size </=5 microm and an antigen loading of approximately 2% (w/w). The analysis by SDS-PAGE electrophoresis of the rSm28GST released from microparticles confirmed the conservation of its physicochemical characteristics. The conservation of the native structure of the entrapped antigen was confirmed by detecting its enzymatic activity after release from microparticles. A single intraperitoneal immunization of mice with rSm28GST entrapped in microparticles resulted in a specific antibody response, which remained high for at least 7 months. The analysis of the isotype profile indicated that immunized mice primarily produced anti-rSm28GST immunoglobulin (Ig) G1 with the coexistence of lower IgG2a and IgG2b levels. Finally, the recognition of the major epitopic regions and the neutralization of the enzymatic activity of the rSm28GST by the antisera confirmed the specificity of the response against the native structure of the antigen. These results confirmed the integrity of the entrapped antigen. Moreover, our results supported the hypothesis that the duration of antigen release is the limiting factor for the duration of antibody production. Indeed, the use of polymers characterized by different molecular weights allowed us to modify the duration of the immune response. Together, these results demonstrated that microencapsulation of an antigen by spray-drying preserved its crucial characteristics required to generate an effective humoral immune response after a single-dose administration.
Baras
B
B
Laboratoire des Relations Hôte-Parasite et Stratégies Vaccinales, INSERM U167, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP-245, F-59019, Lille, France. ipv@pasteur-lille.fr
Benoit
M
M
Poulain-Godefroy
O
O
Schacht
A
A
Capron
A
A
Gillard
J
J
Riveau
G
G
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000008:administration & dosage*; D005260:Female; D005982:Glutathione Transferase / Q000008:administration & dosage* / Q000276:immunology; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D019344:Lactic Acid / Q000008:administration & dosage; D051379:Mice; D011091:Polyesters / Q000008:administration & dosage; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D012550:Schistosoma mansoni / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007106:Immune Sera; D011091:Polyesters; D011108:Polymers; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D005982:Glutathione Transferase