Liposome-based cationic adjuvant formulations (CAF): past, present, and future.
The use of liposomes as vaccine adjuvants has been investigated extensively over the last few decades. In particular, cationic liposomal adjuvants have drawn attention, with dimethyldioctadecylammonium (DDA) liposomes as a prominent candidate. However, cationic liposomes are, in general, not sufficiently immunostimulatory, which is why the combination of liposomes with immunostimulators has arisen as a strategy in the development of novel adjuvant systems in recent years. One such adjuvant system is CAF01. In this review, we summarize the immunological properties making CAF01 a promising versatile adjuvant system, which was developed to mediate protection against tuberculosis (TB) but, in addition, has shown promising protective efficacy against other infectious diseases requiring different immunological profiles. Further, we describe the stabilization properties that make CAF01 suitable in vaccine formulation for the developing world, which in addition to vaccine efficacy, are important prerequisites for any novel TB vaccine to reach global implementation. The encouraging nonclinical data led to a preclinical vaccine toxicology study of the TB model vaccine, Ag85B-ESAT-6/CAF01, that concluded that CAF01 has a satisfactory safety profile to advance the vaccine into phase I clinical trials, which are scheduled to start in 2009.
Christensen
Dennis
D
Vaccine Delivery and Formulation, Department Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Agger
Else Marie
EM
Andreasen
Lars Vibe
LV
Kirby
Daniel
D
Andersen
Peter
P
Perrie
Yvonne
Y
D000276:Adjuvants, Immunologic; D000818:Animals; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000276:immunology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D032581:Tuberculosis Vaccines; C015831:dimethyldioctadecylammonium