Adjuvant properties of non-phospholipid liposomes (Novasomes) in experimental animals for human vaccine antigens.
Non-phospholipid liposomes composed of dioxyethylene cetyl ether, cholesterol 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 antitoxin 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 aluminum phosphate, elicited significantly higher IgG antibodies and antitoxin levels than soluble antigens in mice after a single injection and in rabbits after each of three injections. TT encapsulated in liposomes elicited sustained anti-TT IgG antibody levels in mice after a single injection as compared to TT mixed with liposomes. TT mixed with or encapsulated within liposomes containing monophosphoryl lipid A/squalene or squalene alone, as well as aluminum phosphate adsorbed TT elicited greater primary responses in mice than TT mixed with or encapsulated within plain liposomes. Liposomal TT preparations produced a slightly higher anamnestic response in mice than aluminum phosphate adsorbed TT. Subclass analysis of anti-TT antibodies showed that the majority 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 IgG2a and IgG2b than aluminum phosphate adsorbed or soluble TT. None of the preparations elicited IgG3 or IgM antibodies. It appears that non-phospholipid liposomes are as potent adjuvants as the currently employed adjuvant for human vaccines (aluminum phosphate) or a benchmark adjuvant for experimental immunology (Freund's adjuvant), and may be able to modulate the immune response towards the Th1 type.
Gupta
R K
RK
Massachusetts Public Health Biologic Laboratories, State Laboratory Institute, Boston 02130, USA.
Varanelli
C L
CL
Griffin
P
P
Wallach
D F
DF
Siber
G R
GR
D000276:Adjuvants, Immunologic / Q000032:analysis*; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D004168:Diphtheria Toxoid / Q000008:administration & dosage*; D004337:Drug Carriers; D005260:Female; D007074:Immunoglobulin G; D008081:Liposomes / Q000032:analysis*; D051379:Mice; D011817:Rabbits; D013745:Tetanus Toxoid / Q000008:administration & dosage*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D004168:Diphtheria Toxoid; D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D013745:Tetanus Toxoid