BIODEGRADABLE IMPLANTS FOR THE DELIVERY OF VETERINARY VACCINES - DESIGN, MANUFACTURE AND ANTIBODY-RESPONSES IN SHEEP

Biodegradable implants made from cholesterol and lecithin (C:L) were u sed to deliver a recombinant antigen (recombinant Dichelobacter nodosu s pill) and adjuvant (Quil A) to sheep. Implants (5.5-x1.8-mm) were pl aced subcutaneously and compared to a conventional vaccination regime (2 injections, 4 weeks apart) for antibody responses and tissue compat ibility. Release profiles of antigen and adjuvant were also studied in vitro and in vivo. The presence of Quil A in vaccine implants had a m arked effect on the rate at which antigen was released with 29 and 44% being released in the first 24 h from implants containing pill alone and pill with Quil A, respectively. Sheep produced significant levels of antibody when immunized with implants, however the response was sho rt-lived and of significantly lower intensity than the response stimul ated by two injections of antigen with Quil A (P<0.01). A second impla nt system was developed where implants coated with C:L to delay antige n release, were used in combination with uncoated implants to deliver a priming dose and boosting dose of antigen. Antibody titres stimulate d by the double implant system were equivalent to those stimulated by a conventional regime of two injections (four weeks apart) for the fir st six weeks of the experiment. After this time, antibody levels in th e groups which received implants dropped significantly. In vitro studi es revealed that some of the implant coatings had caused a delay in th e release of antigen (the rate of release peaked at 72 h), however thi s was not long enough to provide a significant boosting effect. In all cases, implants were well tolerated by sheep and caused less local re action than injected vaccines. (C) 1998 Elsevier Science B.V.