title: Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine.
abstract: Advanced contraceptive peptide vaccines suffer from the unavailability of adjuvants capable of enhancing the antibody response with acceptable safety. We sought to overcome this limitation by employing two novel poly(lactic-co-glycolic acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from tetanus toxoid (TT), C-TT2-CTP35: surface-conjugated immunogen to induce phagocytosis; and encapsulated peptide to provide a depot effect, with MgCO(3) co-encapsulated in the polymer to neutralize acidity from the biodegrading PLGA polyester. A single immunization of encapsulated peptide in rabbits elicited a stronger antibody response with equivalent duration relative to a positive control--three injections of the peptide administered in a squalene-based water-in-oil emulsion. Surface-conjugated peptide was less effective but enhanced antibody levels at 1/5 the dose, relative to soluble antigen. Most remarkable and unexpected was the finding that co-encapsulation of base was essential to attain the powerful adjuvant effect of the PLGA-MgCO(3) system, as the MgCO(3)-free microspheres were completely ineffective. A promising contraceptive hCG peptide vaccine with acceptable side effects (i.e., local tissue reactions) was achieved by minimizing PLGA and MgCO(3) doses, without significantly affecting antibody response.
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109-1065, USA.
authors.forename: Chengji
authors.initials: C
authors.lastname: Cui
authors.forename: Vernon C
authors.initials: VC
authors.lastname: Stevens
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schwendeman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006063:Chorionic Gonadotropin / Q000276:immunology; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005079:Excipients; D007114:Immunization; D007267:Injections; D007273:Injections, Intramuscular; D019344:Lactic Acid; D008274:Magnesium / Q000494:pharmacology; D018613:Microscopy, Confocal; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D022642:Vaccines, Contraceptive / Q000009:adverse effects / Q000276:immunology*; D022223:Vaccines, Subunit
chemical_list: D000276:Adjuvants, Immunologic; D006063:Chorionic Gonadotropin; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D022642:Vaccines, Contraceptive; D022223:Vaccines, Subunit; C005479:magnesium carbonate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008274:Magnesium