Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine.
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.
Cui
Chengji
C
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109-1065, USA.
Stevens
Vernon C
VC
Schwendeman
Steven P
SP
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
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