Towards clinical testing of a single-administration tetanus vaccine based on PLA/PLGA microspheres.
The availability of single-administration vaccines would assist in the control of global mortality caused by infectious diseases where protection can be achieved only upon repeated immunisations with appropriate vaccines. Biodegradable microspheres of poly(lactide-co-glycolide) have been studied pre-clinically for this purpose and shown to be promising for several protein and sub-unit antigens. In view of preparing a microsphere-based tetanus vaccine for clinical trials, final candidate vaccine-formulations were pre-clinically optimised here. Specifically, the importance of particular materials and processing for the induction of neutralising antibodies in guinea pigs were examined. The most efficacious vaccines were small-sized (<5 microm), co-adjuvanted with admixed alum and fabricated from fast-degrading polymers. Interestingly, the immunogenicity was less influenced by the type of antigen-stabilising excipient, the number of microsphere populations mixed together, or the microencapsulation technology, i.e. spray-drying versus coacervation, used. On the basis of these, we plan to prepare clinical samples for safety and immunogenicity testing in man.
Johansen
P
P
Institute of Pharmaceutical Sciences, ETH Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland. johansen@pharma.ethz.ch
Estevez
F
F
Zurbriggen
R
R
Merkle
H P
HP
Glück
R
R
Corradin
G
G
Gander
B
B
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D006168:Guinea Pigs; D006801:Humans; D007114:Immunization; D019344:Lactic Acid / Q000008:administration & dosage*; D008863:Microspheres; D011091:Polyesters / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology
D000907:Antibodies, Bacterial; D011091:Polyesters; D011108:Polymers; D013745:Tetanus Toxoid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)