Liposome-based cationic adjuvant formulations (CAF): Past, present, and future

Abstract

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.

Chlamydia muridarum T Cell Antigens and Adjuvants That Induce Protective Immunity in Mice

“…The liposomal surface charge has a major influence on its adjuvant effect. Most in vivo studies demonstrate that cationic liposomes are superior vehicles to anionic and neutral liposomes and the ability of cationic liposomes to target antigens for endocytosis by APCs plays an important role in their delivery properties (9). DDA does not have a direct effect on the maturation of DCs, and the combination of DDA with MPL or TDB delivers the PAMPs to DCs, thereby potentiating immunostimulation.…”

Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response

“…In particular, cationic liposomes based on dimethyldioctadecylammonium (DDA) and trehalose 6,6′-dibehenate (TDB) have been evaluated and show potential as an adjuvant system (designated CAF01) for vaccines [1] given their ability to promote an effective immune response with a strong Th1 response profile. The Th1 response is characterised by secretion of cytokines such as gamma-interferon (IFN-γ), which supports inflammation and activates mainly certain T cells and macrophages, and is thus active in cell mediated immunity.…”

Liposomal delivery of lipoarabinomannan triggers Mycobacterium tuberculosis specific T-cells

“…Besides the well-known adjuvant effects of liposomes on innate immunity [44] this study raises possibilities to improve antigen presentation and T-cell activation. First, the framework structure of the liposomes provides a biochemical matrix that can be modified to improve the targeting, uptake and shuttling of the immunogenic compound into the antigen presenting machinery.…”