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A dual-adjuvanting strategy for peptide-based subunit vaccines against group A Streptococcus: Lipidation and polyelectrolyte complexes
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2020-10-20 , DOI: 10.1016/j.bmc.2020.115823
Lili Zhao 1 , Jieru Yang 1 , Ummey Jannatun Nahar 1 , Zeinab G Khalil 2 , Robert J Capon 2 , Waleed M Hussein 3 , Mariusz Skwarczynski 1 , Istvan Toth 4
Affiliation  

In order to improve the immunogenicity of peptide-based vaccines against group A Streptococcus (GAS), lipid moieties (C16 lipoamino acid and cholic acid) were conjugated with peptide antigen (P25-J8) and further modified with α-poly(glutamic acid) (α-PGA). Thus, positively charged lipopeptide vaccine candidates LCP-1 (P25-K(J8)-SS-C16-C16) and LCP-2 (P25-K(J8)-SS-K(cholic acid)) were synthesized. Negatively charged LCP-3 (P25-K(PGA-J8)-SS-K(cholic acid)) was also produced by attaching α-PGA to the J8 N-terminus of LCP-2. Polyelectrolyte complex (PEC) nanoparticles were formulated with heparin and/or trimethyl chitosan (TMC) for delivery of the lipopeptide vaccine candidates. The ability of the antigen-loaded nanoparticles to induce humoral immune responses was examined in outbred female Swiss mice following intranasal immunization. The antibodies produced were opsonic against all clinical GAS isolates tested.



中文翻译:

针对A组链球菌的基于肽的亚单位疫苗的双重佐治策略:脂质和聚电解质复合物

为了提高针对A组链球菌(GAS)的基于肽的疫苗的免疫原性,将脂质部分(C16脂氨基酸和胆酸)与肽抗原(P25-J8)偶联,并进一步用α-聚谷氨酸修饰(α-PGA)。因此,合成了带正电荷的脂肽疫苗候选LCP-1(P25-K(J8)-SS-C16-C16)和LCP-2(P25-K(J8)-SS-K(胆酸))。带负电荷的LCP-3(P25-K(PGA-J8)-SS-K(胆酸))也通过将α-PGA连接到J8 N-LCP-2的末端。用肝素和/或三甲基壳聚糖(TMC)配制聚电解质复合物(PEC)纳米颗粒,以输送脂肽疫苗候选物。在鼻内免疫后,在近交雌性Swiss小鼠中检查了载有抗原的纳米颗粒诱导体液免疫反应的能力。产生的抗体对所有测试的临床GAS分离物均具有调理作用。

更新日期:2020-10-30
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