Immunogenicity of single-dose diphtheria vaccines based on PLA/PLGA microspheres in guinea pigs.
Biodegradable polyester microspheres (MS) have shown potential for single-dose vaccines. This study examined the immunogenicity of diphtheria toxoid (Dtxd) microencapsulated in different types of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) MS prepared by the methods of spray-drying and coacervation. We investigated the influence of polymer type (PLGA 50:50 of low M(w); PLA of high M(w); end-group stearylated PLAs of low M(w)) and co-encapsulated excipients (BSA and/or trehalose) on Dtxd content, in vitro release and immunogenicity in guinea pigs. The co-encapsulated trehalose lowered the Dtxd entrapment efficiency in the spray-dried particles from 75 to 56%, whereas albumin alone had no effect in the spray-drying, but improved the encapsulation in the coacervation process. With the hydrophobic, end-group stearylated PLAs, Dtxd could only be encapsulated in the presence of albumin. Guinea pigs immunised with Dtxd-MS made with the relatively hydrophilic PLGA 50:50 exhibited specific and sustained antibody responses over 40 weeks, comparable to the responses to alum-adjuvanted toxoid. In contrast, undetectable or very low antibody responses were determined after immunisation with MS made with hydrophobic polymers. Surprisingly, large (15-60 microm) and small (1-5 microm) MS gave comparable primary antibody responses. In conclusion, the data presented confirm the feasibility of MS vaccines to induce strong, long-lasting protective antibody responses after a single immunisation.
Johansen
P
P
Department of Pharmacy, ETH Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland.
Moon
L
L
Tamber
H
H
Merkle
H P
HP
Gander
B
B
Sesardic
D
D
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001672:Biocompatible Materials; D002214:Capsules; D004168:Diphtheria Toxoid / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012995:Solubility; D014614:Vaccines, Synthetic; D014867:Water / Q000737:chemistry
D000907:Antibodies, Bacterial; D001672:Biocompatible Materials; D002214:Capsules; D004168:Diphtheria Toxoid; D011091:Polyesters; D011108:Polymers; D014614:Vaccines, Synthetic; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)