School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Institute of Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Bioorg Med Chem. 2019 Jul 15;27(14):3082-3088. doi: 10.1016/j.bmc.2019.05.033. Epub 2019 May 22.
Short peptides derived from virulent pathogen proteins are promising antigens for the development of vaccines against infectious diseases. However, in order to mimic the danger signals associated with natural infection and stimulate an adaptive immune response, peptide antigens must be co-delivered with immune adjuvants. In this study, a group A streptococcus (GAS) M-protein derived B-cell epitope: J8, and universal T-helper epitope P25 containing peptides, were chemically coupled with different anionic amino acid-based polymers. The poly(anionic amino acid)-peptide antigen conjugates were mixed with trimethyl chitosan (TMC) to produce self-adjuvanting nanoparticulate vaccine candidates. TMC from two different sources were used to analyse their effect on immunogenicity. The nanoparticles produced from a peptide modified with 10 residues of polyglutamic acid and fungal TMC (NP5) stimulated production of the highest levels of serum antibodies in outbred mice. These antibodies were opsonic against all clinical GAS isolates tested.
短肽来源于毒力病原体蛋白是有前途的抗原，为开发疫苗防治传染病。然而，为了模拟与自然感染相关的危险信号，并刺激适应性免疫应答，肽抗原必须与免疫佐剂共同递呈。在这项研究中，A 组链球菌（GAS）M 蛋白衍生的 B 细胞表位：J8，和通用 T 辅助表位 P25 含肽，化学偶联与不同的阴离子氨基酸为基础的聚合物。多（阴离子氨基酸） - 肽抗原缀合物与三甲基壳聚糖（TMC）混合，产生自佐剂纳米颗粒候选疫苗。 TMC 从两个不同的来源进行分析，以分析其对免疫原性的影响。从用聚谷氨酸和真菌 TMC（NP5）修饰的 10 个残基的肽产生的纳米粒子刺激了在外周血小鼠中产生最高水平的血清抗体。这些抗体对所有临床 GAS 分离株均具有调理作用。
