Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination

Abstract

Abstract. Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC 16 ) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC 16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC 16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC 16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam 3 Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.

Modular Peptide Amphiphile Micelles Improving an Antibody-Mediated Immune Response to Group A Streptococcus

“…19,20 In our previous studies, micelles were used as a vaccine delivery vehicle that induced a peptide-specific antibody response. 21 Interestingly, PAMs stimulated a stronger antibody response than peptide alone without the use of an adjuvant making it a self-adjuvanting device. Furthermore, while the hydrophobic tails enhance cell uptake by anchoring into cell membranes, 22 they do not act as pathogen recognition receptor (PRR) agonists and therefore do not function as molecular adjuvants.…”

“…Furthermore, while the hydrophobic tails enhance cell uptake by anchoring into cell membranes, 22 they do not act as pathogen recognition receptor (PRR) agonists and therefore do not function as molecular adjuvants. 21 Rather, it is thought to be the self-assembled, particular-based physical nature of PAMs that affords them immunogenicity. Self-assembly of PAs has the added benefit of being able to facilitate the fabrication of multifunctional heterogeneous micelles through simple mixing of different PAs or other amphiphilic molecules.…”

Recent advances in self-assembled peptides: Implications for targeted drug delivery and vaccine engineering

“…They annealed the micelles at 70 • C to form stable long fibrils while preserving the alpha helical secondary structure. These micelles induced high IgG1 antibody titres without the assistance of TLR-2 receptors in BALB/c mice and HEK-293 cells expressing the TLR-2 receptor [190]. This study demonstrated that micellization of the peptide amphiphiles enhanced the delivery of antigens in their correct conformation.…”

Nanoparticles in Vaccine Delivery

“…This theme issue also includes several original research articles. Tirrell and colleagues report on recent progress in the development of peptide amphiphile micelles that selfadjuvant group A streptococcal vaccinations [9]. In their report, a streptococcus B lymphocyte antigen and a dialkyl hydrophobic moiety were covalently linked and underwent self-assembly into micelles when added to water, due to the hydrophobic interactions among the alkyl tails.…”

“…These include peptide amphiphile micelles [9], pH responsive polymer-based nanoparticles [10], cationic liposomes [11], polysaccharide-based nanoparticles [12], and nanoparticles formed from biodegradable polymers such as p o l y l a c t i c -c o -g l y c o l i d e ( P L G A ) [ 1 3 -1 5 ] and polyanhydrides [16]. This theme issue includes a comprehensive review by Jewell and colleagues on the topic of harnessing biomaterials to engineer the lymph node microenvironment for immunity or tolerance [17].…”