Cationic Peptide Amphiphile Micelles(PAMs) As Nucleic Acid Based Adjuvants Carriers for the Improvement of Subunit Vaccine Efficiency

Molecular adjuvants have been widely used in recent vaccine development due to their excellent ability to stimulate Toll Like Receptors (TLRs) and activate Antigen Presenting Cells (APCs). Nucleic acid based adjuvants such as double stranded RNA polyinsosinic:polycytidylic acid (poly(I:C)) and single strand DNA CpG Oligodexynucleotides (CpG ODNs) are molecular adjuvants that work by mimicking bacterial nucleic acids to stimulate TLRs (TLR-3 and TLR-9, respectively) located in APC endosomes. However, because of their large molecular weight and negative charged backbone, nucleic acid based adjuvants require an effective delivery vehicle to reach their desired site of action.

Peptide amphilphiles (PAs) are a class of diblock biomaterials comprised of hydrophilic peptide(s) conjugated with hydrophobic lipid(s) which self-assemble into peptide amphiphile micelles (PAMs) in water. PAMs have been recently studied for subunit vaccine applications and have shown considerable promise in both prophylactic pathogenic vaccine and therapeutic cancer vaccine studies. For this study, instead of making traditional diblock PAs, we added a third block, oligo(lysine), on the other side of the hydrophobic lipid. When these novel triblock PAs self-assemble, this cationic oligo(lysine) block is exposed yielding cationic PAMs (Cat-PAMs). Due to their significant positive surface charge, Cat-PAMs can readily complex with negatively charged nucleic acid based adjuvants due to electrostatic interactions. Cellular experiments utilizing these micelles show they can effectively deliver nucleic based adjuvants to the endosome of APCs which induces stronger immune responses in vitro and in vivo than conventional vaccine formulations.