Adjuvant efficacy of gelatin particles and microparticles

Abstract

Gelatin particles and microparticles with mean sizes of 2.0 mm and 20.0 μm, respectively, were prepared using different methods. Bovine serum albumin (BSA) was incorporated into them as a model antigen and the immunomodulators lipopolysaccharide (LPS) or muramyldipeptide (MDP) were incorporated into a part of the particles. In vitro tests showed a complete release of BSA after 18 weeks, but its dynamics were different in the two types. Experiments in rabbits demonstrated that the adjuvant activity of the particles administered subcutaneously was equal to that of aluminium hydroxide. Antibodies were detectable at 3 weeks and low levels were demonstrable at 18 weeks after a single administration. Co-incorporation of the immunomodulators LPS or MDP had a favourable effect on both the onset and the intensity of antibody responses. Gelatin microparticles with incorporated BSA were administered to rabbits subcutaneously or orally. Biphasic antibody responses with maxima in weeks 3–6 and in week 20 were found irrespective of the way of administration. The first and the second peaks were higher in the animals treated subcutaneously and orally, respectively. Both groups showed low and approximately equal antibody levels 38 weeks after the immunization. The adjuvant effect of the orally administered microparticles is evidence of their resistance to the proteolytic environment of the digestive tract of rabbits.