Parameters affecting the immunogenicity of microencapsulated tetanus toxoid.
The immunogenic potential of tetanus toxoid (TT) was compared when either adsorbed to aluminium hydroxide (TT-alum) or entrapped in microparticles consisting of poly(D,L-lactic-co-glycolic acid) (PLA:PGA, 55:45) derived polymers. Furthermore, the effect of administering the microparticles in an aqueous buffer or water-in-oil emulsion on the TT immunogenicity was also investigated. When mice were immunized with the different formulations, similar levels of anti-TT antibodies were observed during the primary IgG response. The choice of the carrier seemed to play an important role for both the level and maintenance of the secondary IgG response, attained as a consequence of a booster immunization with TT-alum. The strongest secondary antibody response was obtained by priming with TT-containing microparticles, resuspended in water-in-oil emulsions. As expected, incomplete Freund's adjuvant (IFA) proved to be a more potent adjuvant than peanut oil, whereas resuspension of the microparticles in aqueous solution induced a relatively less efficient antibody response. Overall, microencapsulated TT primed the mice more effectively, since the secondary antibody response was higher and persisted longer compared with TT-alum priming. These results indicate that in addition to TT maintaining its antigenicity after microencapsulation, the microparticles also potentiate its immunogenic properties. This approach should prove very useful for designing more effective vaccines.
Esparza
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I
Department of Drug Delivery Systems, Sandoz Pharma, Basel, Switzerland.
Kissel
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000327:Adsorption; D000534:Alum Compounds; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004339:Drug Compounding; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D014764:Viral Proteins / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D013745:Tetanus Toxoid; D014764:Viral Proteins; C041524:aluminum sulfate