The Immunoadjuvant Action of Liposomes: Optimization Studies

Abstract

One of the liposomal drug carrier aspects under investigation in this laboratory has been enzyme replacement therapy. It had been hoped that administration of (therapeutic) foreign enzymes via liposomes would circumvent immune responses to the enzymes and in collaborative work with A.C. Allison we used diphtheria toxoid as a model foreign protein in mice. Contrary to expectations, however, antitoxoid titres in the sera of the treated mice were much higher than in sera of mice injected with the free toxoid. Thus, the immunoadjuvant properties of liposomes were established (Allison and Gregoriadis, 1974). These initial observations (Allison and Gregoriadis, 1974; Gregoriadis and Allison 1974) were subsequently confirmed and extended with a multitude of antigens relevant to human and veterinary immunization (Gregoriadis, 1985). The list includes Strepto coccus pneumonia serotype 3 (Snippe et al, 1983), Salmonella typhimurium lipopolysaccharide (Desiderio and Campbell, 1985), cholera toxin (Alving et al, 1980; Pierce and Sacci, 1984), adenovirus type 5 hexon (Kramp et al, 1982, Simplex virus type 1 antigens (Naylor et al, 1982), hepatitis B surface antigen (Manesis et al, 1979), Epstein-Barr virus gp 340 protein (Epstein et al, 1985), tetanus toxoid (Davis et al, 1986; Gregoriadis et al, 1987), synthetic peptides of foot-and-mouth disease virus (Francis et al, 1985) and rat spermatozoal polypeptide fraction (Mettler et al, 1983).