ADJUVANT PROPERTIES OF NON-PHOSPHOLIPID LIPOSOMES (NOVASOMES(R)) IN EXPERIMENTAL-ANIMALS FOR HUMAN VACCINE ANTIGENS

Non-phospholipid liposomes composed of dioxyethylene cetyl ether, chol esterol and oleic acid were evaluated as adjuvants with human vaccine antigens, tetanus toxoid (TT) and diphtheria toxoid (DT), in mice and rabbits. Antigens encapsulated in or mixed with liposomes elicited ant itoxin levels similar to those elicited by antigens given with Freund' s adjuvant or adsorbed onto aluminum phosphate. All liposomal antigen preparations, antigen given with Freund's adjuvant or adsorbed onto al uminum phosphate, elicited significantly higher IgG antibodies and ant itoxin levels than soluble antigens in mice after a single injection a nd in rabbits after each of three injections. TT encapsulated in lipos omes elicited sustained anti-TT IgG antibody levels in mice after a si ngle injections as compared to TT mixed with liposomes. TT mixed with or encapsulated within liposomes containing monophosphoryl lipid A/squ alene or squalene alone, as well as aluminum phosphate adsorbed TT eli cited greater primary responses in mice than TT mixed with or encapsul ated within plain liposomes. Liposomal TT preparations produced a slig htly higher anamnestic response in mice than aluminum phosphate adsorb ed TT. Subclass analysis of anti-TT antibodies showed that the majorit y of the antibodies belong to IGG1 subclass. Liposomal TT preparations , particularly those with encapsulated monophosphoryl lipid A/squalene or squalene alone, consistently elicited higher levels of anti-TT IgG 2a and IgG2b than aluminum phosphate adsorbed or soluble TT. None of t he preparations elicited IgG3 or IgM antibodies. It appears that non-p hospholipid liposomes are as potent adjuvants as the currently employe d adjuvant for human vaccines (aluminum phosphate) or a benchmark adju vant for experimental immunology (Freund's adjuvant), and may be able to modulate the immune response towards the Thl type.