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

J Med Chem. 2021 Mar 11;64(5):2648-2658. doi: 10.1021/acs.jmedchem.0c01660. Epub 2021 Feb 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / therapeutic use*
  • Amino Acid Sequence
  • Animals
  • Antigens / therapeutic use
  • Drug Carriers / chemistry
  • Drug Carriers / therapeutic use
  • Female
  • Immunity, Humoral / drug effects
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Peptides / chemical synthesis
  • Peptides / therapeutic use*
  • Streptococcal Vaccines / immunology
  • Streptococcal Vaccines / therapeutic use*
  • Streptococcus pyogenes / drug effects*
  • Streptococcus pyogenes / immunology
  • Vaccines, Subunit

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Drug Carriers
  • Immunoglobulin G
  • Peptides
  • Streptococcal Vaccines
  • Vaccines, Subunit