IRIV-adjuvanted hepatitis A vaccine: in vivo absorption and biophysical characterization.
Immunopotentiating reconstituted influenza virosomes (IRIV) are 150-nm proteoliposomes composed of influenza surface glycoproteins and a mixture of natural and synthetic phospholipids. Due to size, structure and composition of the IRIVs, they serve as an antigen carrier system for efficacious vaccination, as was demonstrated for hepatitis A and influenza. This paper reviews the unique properties of IRIVs and describes the in vivo biodistribution of model antigens using 14C-labeled IRIVs and 125I-labeled streptavidin. IRIV formulated streptavidin induced a strong depot effect after intra muscular (i.m.) vaccination of mice, whereas soluble streptavidin was soon eliminated via the kidney of the animals. A mixture of antigen and IRIVs yielded higher antibody titers after i.m. inoculation than streptavidin alone. The highest immunostimulation was achieved by the binding of the antigen to the investigated adjuvant. The potential penetration of inactivated hepatitis A virions into lipid membranes was assessed by measuring the area increase of a lipid monolayer kept at a constant surface pressure corresponding to that of lipid bilayer vesicles. The monolayers were composed of phosphatidylcholine (POPC) and phosphatidylethanolamine (POPE) (75/25 mol/mol), thus resembling the lipid composition of the IRIV. The results suggested that the hepatitis A antigen may spontaneously bind to the reconstituted IRIV membranes.
Zurbriggen
R
R
Swiss Serum & Vaccine Institute, P.O. Box CH-3001, Berne, Switzerland.
Novak-Hofer
I
I
Seelig
A
A
Glück
R
R
D000042:Absorption; D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006506:Hepatitis A / Q000276:immunology*; D007252:Influenza Vaccines / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D019809:Streptavidin / Q000493:pharmacokinetics*; D014761:Viral Hepatitis Vaccines / Q000493:pharmacokinetics*
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D002250:Carbon Radioisotopes; D007252:Influenza Vaccines; D007457:Iodine Radioisotopes; D014761:Viral Hepatitis Vaccines; D019809:Streptavidin