ENHANCED LYMPH-NODE DELIVERY AND IMMUNOGENICITY OF HEPATITIS-B SURFACE-ANTIGEN ENTRAPPED IN GALACTOSYLATED LIPOSOMES

The purpose of this work is to increase the lymph node delivery and th e immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. HBsAg was entrapped in the dried liposomes with their surfaces modified wit h galactose. Pharmacokinetics and organ distribution of free HBsAg alo ne, HBsAg mixed with aluminum phosphate, HBsAg entrapped in ungalactos ylated liposomes and galactosylated liposomes (Gall) were studied. For each sample, the anti-HBsAg titres were measured by RIA. Most HBsAg i n Gall existed in an antibody-available form. In rats, HBsAg in Gall a dministered to right thigh muscles, resided in the injection sites lon ger than did free HBsAg alone or HBsAg mixed with aluminum phosphate. Also, Gall delivered higher amounts of HBsAg to the regional lymph nod es than did other formulations: the area under the concentration-time curve of HBsAg in the regional lymph nodes given in Gall was 16, 2.4 a nd 2.2-fold higher than that in free form, aluminum phosphate mixture and ungalactosylated liposomes, respectively. The immunogenicity of HB sAg given in Gall showed a good correlation to its enhanced delivery t o the lymph nodes. HBsAg in Gall boosted the formation of antibodies 4 0-fold higher than did free HBsAg, whereas HBsAg mixed with aluminum p hosphate and HBsAg in ungalactosylated liposomes increased the titre b y 21- and 13-fold, respectively. Taken together, it is concluded that the galactosylated liposomes can target HBsAg to the regional lymph no des, rich in the antigen-presenting cells and enhance the immunogenici ty of HBsAg more efficiently than do the conventional aluminum phospha te or the ungalactosylated liposome formulations. (C) 1997 Elsevier Sc ience B.V.