title: An experimental divalent vaccine based on biodegradable microspheres induces protective immunity against tetanus and diphtheria.
abstract: In an endeavor towards development of multivalent vaccines based on biodegradable microspheres, we tested the immunologic performance of several divalent microsphere formulations against tetanus and diphtheria. Microspheres were made by separate microencapsulation of tetanus and diphtheria toxoid in poly(lactide-co-glycolide) by either spray-drying or coacervation. Guinea pigs were subcutaneously immunized by a single injection of the divalent vaccines or, for control, an equivalent dose of a licensed vaccine containing both antigens adsorbed on aluminium hydroxide. All microsphere formulations were strongly immunogenic, irrespective of particle size and hydrophobicity. End point titers of ELISA antibodies, mainly of the IgG1 subtype, were comparable to those obtained after immunization with the licensed vaccine. The microspheres provided increasing levels of antibodies, during the 16 weeks of testing, and the antibodies were weakly polarized towards tetanus. The induced antibodies were also toxin neutralizing, as determined for both diphtheria (1-4 IU/mL) and tetanus (5-9 IU/mL) 8 weeks after immunization. These neutralization levels were several orders of magnitude above the level considered minimum for protection (0.01 IU/mL). When the animals were challenged with tetanus or diphtheria toxins 6 weeks after immunization, microsphere vaccines produced protective immunity that was comparable to or better than that induced by the licensed divalent vaccine. In conclusion, this study showed that a single administration of biodegradable microsphere vaccines provided protective immunity against diphtheria and tetanus, and that this immunization approach might be feasible for multivalent vaccines.
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Controls, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Marisa
authors.initials: M
authors.lastname: Peyre
authors.forename: Dorothea
authors.initials: D
authors.lastname: Sesardic
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D002626:Chemistry, Pharmaceutical; D004165:Diphtheria / Q000276:immunology / Q000517:prevention & control; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008863:Microspheres; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D022422:Diphtheria-Tetanus Vaccine