Immunostimulation by Synthetic Lipopeptide-Based Vaccine Candidates: Structure-Activity Relationships

Abstract

Peptide-based vaccines offer several advantages over conventional whole organism or protein approaches by offering improved purity and specificity in inducing immune response. However, peptides alone are generally non-immunogenic. Concerns remain about the toxicity of adjuvants which are critical for immunogenicity of synthetic peptides. The use of lipopeptides in peptide vaccines is currently under intensive investigation because potent immune responses can be generated without the use of adjuvant (thus are self-adjuvanting). Several lipopeptides derived from microbial origin, and their synthetic versions or simpler fatty acid moieties impart this self-adjuvanting activity by signaling via Toll-like receptor 2 (TLR2). Engagement of this innate immune receptor on antigen-presenting cell leads to the initiation and development of potent immune responses. Therefore optimization of lipopeptides to enhance TLR2-mediated activation is a promising strategy for vaccine development. Considerable structure-activity relationships that determine TLR2 binding and consequent stimulation of innate immune responses have been investigated for a range of lipopeptides. In this mini review we address the development of lipopeptide vaccines, mechanism of TLR2 recognition, and immune activation. An overview is provided of the best studied lipopeptide vaccine systems.

A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein

“…In fact, Coa-ASC16 is formed by an ester, which to date has not been described as a PAMP. Nevertheless, it has been previously shown that one of its components, palmitic acid, can activate TLR2 and TLR4 [43][44][45]. In contrast, our results indicate that neither TLR2 nor TLR4 was involved in the inflammatory response induced by Coa-ASC16.…”

Skin-Specific Unsaturated Fatty Acids Boost the Staphylococcus aureus Innate Immune Response

“…Particularly synthetic lipopeptides have been extensively studied, as they have strong adjuvant activity and are also potential vaccine candidates (56)(57)(58). The self-adjuvanting effect of lipopeptides was demonstrated to act through stimulation of TLR2 and dendritic cell (DC) activation (59,60). By screening a combinatorial lipohexapeptide collection based on synthetic Pam3Cys-lipopeptides in an in vitro IL-8 induction assay, it has been demonstrated that both the peptide sequence and the lipid moiety influence signaling (56).…”

Therapeutic cyclic lipopeptides mining from microbes: latest strides and hurdles

“…It indicated the possibility of potent vaccine development using the surfactin (Pan et al 2014). The development of lipopeptide vaccines, their TLR2 recognition and immune activation mechanism have been reviewed (Zaman and Toth 2013). Design of therapeutic human papilloma virus (HPV) vaccines using lipoimmunogens was met with considerable success (Shen et al 2015).…”