Gemini lipopeptides as vaccine adjuvants: a new role for these versatile carriers

Abstract

Brief communication Vaccines are one of the most significant interventions of medicine, and showed important progress from empirical formulations to rational designs, along the time. Nevertheless, adjuvant development did not experience similar progress [1]. Oligonucleotides containing non-methylated CpG sequences (CpG-ODN) are immunostimulant molecules that are added in vaccine formulations as adjuvants, mostly as phosphorothioate modified ODN (PS-CpG-ODN). These types of bonds give resistance to nucleases leading to a longer in vivo persistence than natural phosphodiester ODN (PO-CpG-ODN). However, the cost of production of PS-CpG-ODN is higher than PO-CpG-ODN, and it has been reported that the long-term use of modified ODN may be associated with adverse side effects in mice, and primates [2]. Those are important factors to consider when developing vaccine systems. Nevertheless, PO-CpG-ODN can be used as adjuvant if complexed with an adequate vehicle, as liposomes [3,4]. Gemini compounds are amphipathic molecules formed by a hydrophobic moiety containing two hydrocarbon chains of variable length, and two hydrophilic portions that can be peptides, among other low molecular weight groups [5]. We developed a series of monomeric lipopeptides that function as DNA and protein carriers, called [AGn-Cm]2, where AGn is the peptidic polar head group and Cm is the non-polar region, attached to the peptide N-terminus [5]. A cysteine in the peptide can form a disulphide bridge with another monomer and generates the gemini lipopeptide by dimerization at physiological pH. Based on their ability to form complexes with negatively charged DNA, some of them are transfection reagents with high efficiency [5,6]. However, the use of these molecules in adjuvant formulations has not been described. In this study, we developed formulations based on cationic gemini lipopeptides and

Gemini Lipopeptide Bearing an Ultrashort Peptide for Enhanced Transfection Efficiency and Cancer-Cell-Specific Cytotoxicity

“…Cationic gemini lipopeptides are a relatively new class of amphiphilic structures, where two monomeric peptide−lipid conjugates are connected by a spacer. 24,25 These new types of molecules along with other conventional lipopeptides have been utilized for antimicrobial testing, 26,27 but their use in gene delivery is very rare. Damen et al utilized an ultrashort (serine−proline−lysine−arginine) peptide containing a lipopeptide to deliver DNA and siRNA.…”

“…Despite several efforts that have been made to develop efficacious liposomal formulations for gene delivery, there still exists a strong and persistent need for novel gene carriers that address the issues affecting safe and efficient cellular delivery. Cationic gemini lipopeptides are a relatively new class of amphiphilic structures, where two monomeric peptide–lipid conjugates are connected by a spacer. , These new types of molecules along with other conventional lipopeptides have been utilized for antimicrobial testing, , but their use in gene delivery is very rare. Damen et al utilized an ultrashort (serine–proline–lysine–arginine) peptide containing a lipopeptide to deliver DNA and siRNA .…”