Cationic liposomes containing mycobacterial lipids: a new powerful Th1 adjuvant system.
The immunostimulation provided by the mycobacterial cell wall has been exploited for many decades, e.g., in Freund's complete adjuvant. Recently, the underlying mechanism behind this adjuvant activity, including Toll receptor signaling, has begun to be unraveled, confirming the potential of mycobacterial constituents to act as adjuvants. In this study, the immunostimulatory properties of a Mycobacterium bovis BCG lipid extract were tested for their adjuvant activity. Administration of the lipids in dimethyl dioctadecyl ammonium bromide-based cationic liposomes induced a powerful Th1 response characterized by markedly elevated antigen-specific immunoglobulin G2a (IgG2a) isotype antibodies and substantial production of gamma interferon. The adjuvant formulation (designated mycosomes) elicited high levels of gamma interferon both in C57BL/6 as well as in Th2-prone BALB/c mice. Furthermore, the mycosomes induced immune responses to protein antigens from several sources including Mycobacterium tuberculosis, Chlamydia muridarum, and tetanus toxoid. In a tuberculosis challenge model, the mycosomes combined with the Ag85B-ESAT-6 fusion protein were demonstrated to have a unique ability to maintain sustained immunological memory at a level superior to live BCG.
Rosenkrands
Ida
I
Statens Serum Institut, Department of Infectious Disease Immunology, Adjuvant Research, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
Agger
Else Marie
EM
Olsen
Anja W
AW
Korsholm
Karen S
KS
Andersen
Claire Swetman
CS
Jensen
Klaus T
KT
Andersen
Peter
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D001426:Bacterial Proteins; D002855:Chromatography, Thin Layer; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D008055:Lipids; D008081:Liposomes