Towards clinical testing of a single-administration tetanus vaccine based on PLA/PLGA microspheres

The availability of single-administration vaccines would assist in the cont rol of global mortality caused by infectious diseases where protection can be achieved only upon repeated immunisations with appropriate vaccines. Bio degradable 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 vac cine for clinical trials, final candidate vaccine-formulations were pre-cli nically optimised here. Specifically, the importance of particular material s and processing for the induction of neutralising antibodies in guinea pig s were examined. The most efficacious vaccines were small-sized(< 5 <mu>m), co-adjuvanted with admired alum and fabricated from fast-degrading polymer s. Interestingly, the immunogenicity was less influenced by the type of ant igen-stabilising excipient, the number of microsphere populations mixed tog ether, or the microencapsulation technology, i.e. spray-drying versus coace rvation, used. On the basis of these, we plan to prepare clinical samples f or safety and immunogenicity testing in man. (C) 2000 Elsevier Science Ltd. All rights reserved.