Abstract
This study describes a new fat-based vehicle (liposphere) that has been developed as a carrier for vaccines. Manufacture of lipospheres is accomplished by gently meltiag neutral fat in the presence of phospholipid and antigen, and then dispersing the melted mixture in an aqueous suspension by vigorous shaking. Upon cooling of this mixture a phospholipid-stabilized solid
hydrophobic fat core containing antigen forms spontaneously. A typical composition of the lipid phase of the lipospheres consists of a neutral fat, such as tristearin or ethylstearate, and a phospholipid such as le-ithin. A recombinant malaria antigen, R32NSi, containing epitopes derived from the circumsporozoite protein of Plasmodium falciparttm, was incorporated in lipospiher,, together with lipid A as an adjuvant. After intramuscular injection of the formulation in rabbits, high levels of specific IgG antibodies to the antigen were still present 12
weeks after primary immunization. Several chemical and physical parameters that might be expected to influence the liposphere vaccine formulation were investigated. The particle size distribution of lipospheres depended on the fat to phospholipid (F/P1.) molar ratio, and the immune response to liposphere-encapsulated R32NSI was also dependent on the F/PL, ratio. For F/PL, ratios of _- 0.75 most of the lipospheres had an average diameter of less than 10 [im.
while at F/PL ratios of : 2.5 approximately 80% of the particles had an average size of 73 gim. Among the ratios tested, a maximal level of lg(; antibody production was obtained at a F/Pl. ratio of 0.75, while at larger ratios decreased antibody production was observed. The effects of antigen dose and phospholipid composition were also examined.
hydrophobic fat core containing antigen forms spontaneously. A typical composition of the lipid phase of the lipospheres consists of a neutral fat, such as tristearin or ethylstearate, and a phospholipid such as le-ithin. A recombinant malaria antigen, R32NSi, containing epitopes derived from the circumsporozoite protein of Plasmodium falciparttm, was incorporated in lipospiher,, together with lipid A as an adjuvant. After intramuscular injection of the formulation in rabbits, high levels of specific IgG antibodies to the antigen were still present 12
weeks after primary immunization. Several chemical and physical parameters that might be expected to influence the liposphere vaccine formulation were investigated. The particle size distribution of lipospheres depended on the fat to phospholipid (F/P1.) molar ratio, and the immune response to liposphere-encapsulated R32NSI was also dependent on the F/PL, ratio. For F/PL, ratios of _- 0.75 most of the lipospheres had an average diameter of less than 10 [im.
while at F/PL ratios of : 2.5 approximately 80% of the particles had an average size of 73 gim. Among the ratios tested, a maximal level of lg(; antibody production was obtained at a F/Pl. ratio of 0.75, while at larger ratios decreased antibody production was observed. The effects of antigen dose and phospholipid composition were also examined.
| Original language | English |
|---|---|
| Place of Publication | Washington, DC |
| Publisher | Defense Technical Information Center |
| Number of pages | 13 |
| State | Published - 1992 |