Immunomodulatory Peptide Amphiphile Micelles for Prophylactic Vaccination

Peptide amphilphiles (PAs) are a class of di-block materials comprised of hydrophilic peptide head(s) and hydrophobic tail(s) which self-assemble into peptide amphiphile micelles (PAMs) in water. PAMs have shown their great ability in biomedical applications. More recently, PAMs are studied for the application of prophylactic vaccines.

This study demonstrates that micelle vaccines’ physical properties such as size, shape, and surface charge are controllable by chemical modification. These different physical properties have shown different abilities to interact with biological systems. For instance, these interactions include different cell uptake ability by Antigen Presenting Cells(APCs), immunogenicity, and cytotoxicity. These discoveries will help the future design of prophylactic vaccines.

Vaccine adjuvants are vaccine agonists that can help the body produce protection. Molecular adjuvants are a type of adjuvants that can stimulate Toll Like Receptors (TLRs) on APCs. Studies have shown that co-delivery of antigen and adjuvants can produce desirable immune responses, so numerous research has been done to associate antigen and molecular adjuvant utilizing engineering methods. This study compares two co-delivery strategies of the model ovalbumin antigen peptide and the TLR-2 agonist Pam₂C, a lipid based adjuvant, either chemically linking with Pam₂C and antigen to form micelles (strong association force), or entrap Pam₂C in antigen micelles (weaker association force). Surprisingly, the stronger chemical association between antigen and Pam₂C yielded lower immunogenicity both in vitro and in vivo. This may lead to more extensive studies on the topic of the co-delivery of antigen and adjuvant for vaccine research.