(719f) Improved Vaccination Through the Use of Self-Assembled Peptide Amphiphile Micelle Delivery Devices

Whole-killed and live-attenuated vaccines have been tremendously effective in preventing pathogenic infections, but can be associated with undesirable side effects. Subunit vaccines that deliver just the peptide antigen of interest have been shown capable of stimulating an immune response, but are generally weak immunogens on their own requiring strong adjuvants (non-specific immunostimulants) to be effective. In order to enhance the immunogenicity of peptide vaccines, new delivery systems must be designed.

Peptide amphiphiles are unique biomaterials consisting of a hydrophilic peptide conjugated to a hydrophobic lipid or fatty acid tail that undergo self-assembly into micelles in water. Micellization is driven by the need to shield the hydrophobic tail from the aqueous surroundings leading to a micelle comprised of a hydrophobic tail core and a hydrophilic peptide corona. Peptide amphiphile micelles allow for the presentation of hundreds to tens of thousands of peptide on the surface of each micelle. Peptide amphiphile micelles also crowd peptides within their coronas providing an artificial tertiary structure which induces desirable peptide secondary structure conformations. Since peptide vaccines are often delivered in low local concentrations, peptide amphiphile micelles provide a novel platform to improve the host immune response to peptide vaccines.

A conformational B cell epitope (J8) of Group A Streptococcus, the bacterial causative agent of diseases ranging from mild pharyngitis to severe toxic shock syndrome, was chosen to evaluate the immunostimulatory effect of peptide amphiphile micelles. J8 was covalently tethered to a di-palmitic acid tail (J8-diC₁₆) and fabricated into peptide amphiphile micelles in water. When delivered to mice subcutaneously, J8-diC₁₆ was found to induce J8-specific high antibody titers greater than soluble J8 delivered with a commercially available adjuvant. To further enhance the antibody response, mixed micelles comprised of J8-diC₁₆ and amphiphilic adjuvants were synthesized. Mixed micelles induced a strong immune response after a single vaccination and higher titers than all other formulations regardless of the vaccine regimen. These results provide significant evidence that peptide amphiphile micelles are innovative constructs capable of enhancing the immunogenicity of peptide vaccine candidates.