Development and Evaluation of CAF01

There is a need for designing vaccine adjuvants that prime T-cell immunity for effective vaccines against intracellular pathogens such as Mycobacterium tuberculosis, Chlamydia trachomatis, and Plasmodium falciparum. One such adjuvant, CAF01, has an exceptional ability to induce memory CD4 T-cell responses, shown in both mice and humans. CAF01 consists of liposomes formed of N,N'-dimethyl-N,N'-dioctadecylammonium (DDA) stabilized with the synthetic mycobacterial immunomodulator α,α′-trehalose 6,6′-dibehenate (TDB). DDA acts as a delivery vehicle serving to promote uptake and presentation of the vaccine antigen in the relevant subset of antigen-presenting cells (APCs), whereas TDB is a Mincle ligand that activates APCs through the SYK-CARD9 signaling pathway thereby inducing highly potent Th1/Th17 and B-cell responses. The safety and immunogenicity of CAF01 have been documented in human clinical trials and indicate that CAF01 is ready for further clinical development in novel human or animal vaccines in which cellular and humoral immune responses are required.