Oral immunisation with peptide and protein antigens by formulation in lipid vesicles incorporating bile salts (bilosomes).
The ability of non-ionic surfactant vesicles to induce systemic immune responses in mice following oral immunisation was studied using a standard antigen (bovine serum albumin), a synthetic measles peptide and an influenza sub-unit vaccine. The effectiveness of this formulation was significantly increased by incorporating bile salts (in particular deoxycholate) into the formulation. We have named the resulting vesicles bilosomes. We found that the most effective immunisation protocol was to give two doses of vaccine three days apart and then repeat this protocol two weeks later. Following this method, preparation of measles peptide in bilosomes produced a specific cell mediated response, as measured by splenocyte proliferation and IL-2 production. Of particular significance, these studies demonstrate that oral administration of bilosomes incorporating the influenza sub-unit vaccine could induce as potent an antibody response as the parenterally administered vaccine containing the same quantity of antigen. In addition, the Th1/Th2 balance, as measured by antibody subclasses, was similar whether animals were immunised by the oral or the parenteral vaccine route. As bilosomes are prepared from naturally occurring lipids and have no apparent toxicity associated with their use, they represent a useful modification of conventional lipid vesicle based systems for the oral delivery of proteins and peptides.
Conacher
M
M
Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK.
Alexander
J
J
Brewer
J M
JM
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D001647:Bile Acids and Salts / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008055:Lipids / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012710:Serum Albumin, Bovine / Q000276:immunology
D000941:Antigens; D001647:Bile Acids and Salts; D007074:Immunoglobulin G; D007376:Interleukin-2; D008055:Lipids; D016753:Interleukin-10; D012710:Serum Albumin, Bovine