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CATEGORY: VACCINES & THERAPEUTICS ADJUVANTS: IMMUNOSTIMULATORY Adjuvants: Immunostimulatory Rebecca Helson, London, UK Monophosphoryl lipid A (MPL) MPL is a non-toxic component derived from lipopolysaccharide (LPS) of bacterial cell walls and interacts with TLR-4 and TLR-2, inducing a Th1-skewed response. MPL is thought to directly activate macrophages resulting in the induction of IFN-γ and IL-2. However, it is not as potent at inducing antibody responses. Unmethylated CpG dinucleotides Unmethylated CpG dinucleotides are recognised by the innate immune system, as they are underrepresented and methylated in vertebrate DNA. The immune response to unmethylated CpG has been linked in humans to the activation of TLR-9. Interactions result in the maturation of dendritic cells, upregulation of MHC class II to produce professional antigen presenting cells, induction of Th1 cytokines and triggering B-cell proliferation. Saponins Saponins are derived from the bark of a Chilean tree, Quillaja sponaria, so unlike other immunostimulatory adjuvants, is not pathogen derived. A highly purified fraction called QS21 is a potent adjuvant for the induction of a Th1-dominated response, including CTLs. Saponins are thought to form pores in cell membranes that allow antigens to gain access to the endogenous presentation pathway resulting in presentation by MHC class I and hence CTL activation. Cytokines Cytokines can also be used directly to modify or redirect the immune response. However as they are proteins, they have a short half life and, are generally very expensive. © The copyright for this work resides with the author Immune-potentiating adjuvants are thought to activate the innate immune system via toll-like receptors (TLRs) or pattern recognition receptors (PRR). Cooperation between these two components is desirable in directing the balance of humoral and cell-mediated immunity associated with the acquired immune response.