Polyphenylalanine as a self-adjuvanting delivery system for peptide-based vaccines: the role of peptide conformation

Peptide-based vaccines are composed of minimal microbial components that are required to stimulate immune responses. Peptide antigens are easy to produce, relatively cheap and nontoxic. They are also able to activate the immune system in a well-controlled manner. However, peptides themselves are poor immunogens and have to be co-administered with an adjuvant (immune stimulator) to produce desired immune responses. Unfortunately, many adjuvants are toxic, poorly effective or not compatible with peptide antigens. Recently, we demonstrated that, upon conjugation to a peptide antigen, poly(hydrophobic amino acids) can self-assemble into nanoparticles and induce strong humoral immune responses. Here, we examine the ability of polyphenylalanine to act as a self-adjuvanting moiety when conjugated to a peptide antigen derived from Group A Streptococcus M-protein. The polyphenylalanine moiety was further lipidated to alter the conjugate conformation and its ability to form nanoparticles. The lipidated analogue triggered the production of a high level of antibodies in immunized mice. The antibodies produced were highly opsonic against tested GAS clinical isolates.