Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Streptococcus Vaccine Delivery

Peptide antigens have been widely used in the development of vaccines, especially for those against auto-immunity-inducing pathogens and cancers. However, peptide-based vaccines require adjuvant and/or a delivery system to stimulate desired immune responses. Here, we explored the potential of self-adjuvanting poly(hydrophobic amino acids) (pHAAs) to deliver peptide-based vaccine against Group A Streptococcus (GAS). We designed and synthesized self-assembled nanoparticles with a variety of conjugates bearing a peptide antigen (J8-PADRE) and polymerized hydrophobic amino acids to evaluate the effects of structural arrangement and pHAAs properties on a system's ability to induce humoral immune responses. Immunogenicity of the developed conjugates was also compared to commercially available human adjuvants. We found that a linear conjugate bearing J8-PADRE and 15 copies of leucine induced equally effective, or greater, immune responses than commercial adjuvants. Our fully defined, adjuvant-free, single molecule-based vaccine induced the production of antibodies capable of killing GAS bacteria.

Automated summary

The study demonstrates the potential of self-adjuvanting poly(hydrophobic amino acids) as a delivery system for peptide-based vaccines against Group A Streptococcus (GAS). Conjugates with a linear arrangement of J8-PADRE and leucine were found to induce equally effective or even better immune responses compared to commercial adjuvants. The developed adjuvant-free vaccine based on single molecule successfully elicited antibodies capable of killing GAS bacteria.