School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
J Med Chem. 2021 Mar 11;64(5):2648-2658. doi: 10.1021/acs.jmedchem.0c01660. Epub 2021 Feb 2.
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 (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.
肽抗原已被广泛应用于疫苗的开发，特别是针对自身免疫诱导病原体和癌症的疫苗。然而，基于肽的疫苗需要佐剂和/或递送系统来刺激所需的免疫反应。在这里，我们探索了自佐剂聚（疏水性氨基酸）（pHAAs）递送针对 A 组（GAS）的肽基疫苗的潜力。我们设计并合成了具有多种缀合物的自组装纳米粒子，这些缀合物带有肽抗原（J8-PADRE）和聚合疏水性氨基酸，以评估结构排列和 pHAAs 性质对系统诱导体液免疫反应能力的影响。还比较了开发的缀合物与市售的人类佐剂的免疫原性。我们发现，带有 J8-PADRE 和 15 个亮氨酸的线性缀合物诱导的免疫反应与商业佐剂同样有效，甚至更强。我们完全定义的、无佐剂的、基于单一分子的疫苗诱导产生了能够杀死 GAS 细菌的抗体。
