The Development of Linear and Cyclic Lipopeptide based Adjuvants (#142)
Vaccination is the most efficient medical invention to counter the effects of infectious diseases. Peptide subunit vaccines utilises selected microbial fragments and were developed to eliminate toxicity related-issues associated with conventional vaccines [1]. However, peptide antigens are poorly immunogenic, and it requires the aid of an adjuvant to enhance the immunogenicity and provide long-term protective immunity [2]. Lipids have been known to act as an adjuvant once conjugated to the antigen for peptide subunit vaccines. Moreover, lipidation assists in peptide vaccine delivery to increase bioavailability, chemical stability and protection against enzymatic degradation [3]. The lipopeptide adjuvants used in this study were designed based on lipid core peptide (LCP) [4], antimicrobial peptides (AMPs) [5] and short cationic peptides to investigate the ability of these compounds to stimulate an immune response against the co-administered antigen. J8 (B-cell epitope derived from Group A Streptococcus) and p25 (Universal T-cell epitope) were chosen as a model antigen. A series of lipopeptide adjuvant analogues were successfully synthesised through Microwave-assisted Solid Phase Peptide Synthesis (SPPS) (Boc and Fmoc strategy) with high yield and purity. They were able to self-assemble into nanoparticles ranging from 100 nm to 1000 nm. The nanoparticles were found to be stable at RT. Finally, the mice were immunised the nanoparticles and GAS antigen as an active physical mixture. It was delivered through the subcutaneous route to examine their ability to stimulate systemic and mucosal immune response.
- Skwarczynski M, Zaman M, Toth I: Lipo-Peptides/Saccharides for Peptide Vaccine Delivery. In: Handbook of Biologically Active Peptides. 2013: 571-579.
- Coffman RL, Sher A, Seder RA: Vaccine adjuvants: putting innate immunity to work. Immunity 2010, 33(4):492-503.
- Bartlett S, Skwarczynski M, Toth I: Lipids as activators of innate immunity in peptide vaccine delivery. Curr Med Chem 2018.
- Skwarczynski M, Toth I: Recent advances in peptide-based subunit nanovaccines. Nanomedicine 2014, 9(17):2657-2669.
- Bechinger B, Gorr SU: Antimicrobial Peptides: Mechanisms of Action and Resistance. J Dent Res 2017, 96(3):254-260.