title: Pluronic F127-based systemic vaccine delivery systems.
abstract: We have developed a vaccine delivery system based on the non-ionic block copolymer, Pluronic F127 (F127), combined with selected immunomodulators. F127-based matrices are characterized by a phenomenon known as reverse thermogelation, whereby the formulation undergoes a phase transition from liquid to gel upon reaching physiological temperatures. Protein antigens (tetanus toxoid (TT), diphtheria toxoid (DT) and anthrax recombinant protective antigen (rPA)) were formulated with F127 in combination with CpG motifs or chitosan, as examples of immunomodulators, and were compared to more traditional adjuvants in mice. IgG antibody responses were significantly enhanced by the F127/CpG and F127/chitosan combinations compared to antigens mixed with CpGs or chitosan alone. In addition, the responses were significantly greater than those elicited by aluminum salts. Furthermore, the functional activity of these antibodies was demonstrated using either in vivo tetanus toxin challenge or an anthrax lethal toxin neutralization assay. These studies suggest that a block-copolymer approach could enhance the delivery of a variety of clinically useful antigens in vaccination schemes.
authors.affiliation: RxKinetix Inc., 1172 Century Drive Suite 260, Louisville, CO 80027, USA. ccoeshott@rxkinetix.com
authors.forename: Claire M
authors.initials: CM
authors.lastname: Coeshott
authors.forename: S Louise
authors.initials: SL
authors.lastname: Smithson
authors.forename: Evie
authors.initials: E
authors.lastname: Verderber
authors.forename: Adrian
authors.initials: A
authors.lastname: Samaniego
authors.forename: Joan M
authors.initials: JM
authors.lastname: Blonder
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Rosenthal
authors.forename: M A Julie
authors.initials: MA
authors.lastname: Westerink
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002686:Chitin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000276:immunology; D048271:Chitosan; D004166:Diphtheria Antitoxin / Q000096:biosynthesis; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology; D016503:Drug Delivery Systems; D004357:Drug Synergism; D051379:Mice; D008807:Mice, Inbred BALB C; D020442:Poloxamer / Q000008:administration & dosage; D013743:Tetanus Antitoxin / Q000096:biosynthesis; D013745:Tetanus Toxoid / Q000008:administration & dosage; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D004166:Diphtheria Antitoxin; D004168:Diphtheria Toxoid; D013743:Tetanus Antitoxin; D013745:Tetanus Toxoid; D014612:Vaccines; D020442:Poloxamer; D002686:Chitin; D048271:Chitosan