Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A <i>Streptococcus</i> Vaccine Delivery
Armira Azuar, Zhuoqing Li, Mohini A. Shibu, Lili Zhao, Yacheng Luo, Ahmed O. Shalash, Zeinab G. Khalil, Robert J. Capon, Waleed M. Hussein, István Tóth, Mariusz Skwarczyński
Abstract
Peptide antigens have been widely used in the development of vaccines, especially for those against autoimmunity-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.