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

Abstract

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.