A novel positively-charged lipid 1,2-bis(hexadecylcycloxy)-3-trimethyl aminopropane (BisHOP) enhances the adjuvant effect of liposomes on encapsulated tetanus toxoid.

A novel positively charged lipid, 1,2-bis(hexadecylcycloxy)-3-trimethylaminopropane-HCl (BisHOP), when incorporated into the bilayers of phosphatidylcholine (PC) and distearoyl phosphatidylcholine (DSPC) dehydration-rehydration vesicles (DRV), was shown to have a powerful effect in enhancing the IgG1 response to tetanus toxoid encapsulated within the liposomes. The adjuvant effect was significantly greater when 20% BisHOP was incorporated as compared to 10% incorporation and to control PC and DSPC DRV. Plain, uncharged DSPC DRV were found to have a greater adjuvant effect than plain PC DRV on the entrapped tetanus toxoid after a single intramuscular injection. Even though antibody levels at 8 weeks post-injection were similar for 20% BisHOP PC and DSPC DRV, the rate of rise of antibody titres was more rapid for 20% BisHOP DSPC than for 20% BisHOP PC DRV. These results suggest that faster and higher titers of antibodies may be obtained by optimal manipulation of the charged and non-charged lipid components of liposomes.

Comparison of the immune response against polio peptides covalently-surface-linked to and internally-entrapped in liposomes.

The adjuvanticity of liposomes on two different modes of presentation of polio virus subunit peptides was demonstrated by incorporating the poorly immunogenic synthetic polio peptides, W1 and W2, into the internal space of and covalently-linked to the surface of dehydration-rehydration vesicles (DRV). It was found that for both peptides, liposome association in either mode boosted the primary and secondary IgG1 responses against 5 micrograms peptide as compared to controls in which free peptide was administered. Surface-linkage of peptides (both W1 and W2) exhibited an initially more rapid rise in antibody levels, as compared to internal entrapment of the peptides, but elicited no observable secondary response. However, although encapsulated W1 showed a milder primary response when compared to the surface-linked formulation, it later elicited a strong secondary response. These results suggested that it may be advantageous to administer liposomal virus subunit vaccines in both surface-linked and internally entrapped formulations to achieve adequate initial antibody levels followed by an anamnestic response.