The application of biodegradable collagen minipellets as vaccine delivery vehicles in mice and sheep.

Collagen minipellets are injectable delivery vehicles that release antigen and adjuvant over several days in a first-order release profile. In vaccination experiments in mice, secondary antibody responses induced by minipellets formulated with avidin and IL-1beta as adjuvant were equivalent to those induced by a conventional immunization with avidin in alum. When no adjuvant was used, anti-avidin responses induced by minipellets were 10-20-fold higher than those induced by injection of avidin in saline. In sheep, conventional vaccination with avidin in alum induced antibody responses initially exceeding that induced by minipellets formulated with avidin and IL-1beta, while following a secondary vaccination, the minipellet antibody response was equal to or greater than the alum-adjuvanted control groups. Increasing levels of IL-1beta adjuvant resulted in enhanced persistence of the antibody response. When clostridial vaccine antigens were incorporated into the minipellets, total antibody responses induced in sheep were equivalent to those induced by vaccination with the clostridial antigens in alum. Neutralizing antibody titres exceeded those induced by conventional vaccination. No adverse site reactions were observed at the implant site, with immunohistological study showing that the cellular infiltrate was dominated by a transient influx of neutrophils. This is a typical response to delivery of bioactive IL-1beta. The minipellets were completely degraded within 35 days of implantation.