1. Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Streptococcus Vaccine Delivery
- Author
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Mariusz Skwarczynski, Istvan Toth, Zhuoqing Li, Zeinab G. Khalil, Yacheng Luo, Waleed M. Hussein, Ahmed O. Shalash, Robert J. Capon, Armira Azuar, Mohini A Shibu, and Lili Zhao
- Subjects
chemistry.chemical_classification ,0303 health sciences ,Streptococcus vaccine ,biology ,Chemistry ,medicine.medical_treatment ,Immunogenicity ,Peptide ,01 natural sciences ,0104 chemical sciences ,Amino acid ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,Immune system ,Antigen ,Biochemistry ,Drug Discovery ,medicine ,biology.protein ,Molecular Medicine ,Antibody ,Adjuvant ,030304 developmental biology - 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.
- Published
- 2021
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