Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates
Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates
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DOI：
10.1016/j.bmc.2016.03.063
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发表时间：
2016-07-15
影响因子：
3.5
通讯作者：
Toth, Istvan
中科院分区：
文献类型：
--
作者：
Chan, Amy;Hussein, Waleed M.;Toth, Istvan
感染A组链球菌(GAS)可导致一系列不同的疾病，其中一些是致命的。目前，我们致力于开发一种针对GAS的疫苗，主要集中在脂质核心肽(LCP)系统，这是一种含有脂氨基酸(LAA)部分的亚单位疫苗，可以刺激全身抗体活性。在本研究中，来自GAS M蛋白的代表B细胞表位的多肽(J14)与通用T辅助表位(P25)一起被整合在四个不同空间取向或LAA长度的LCP结构中。通过构效关系研究发现，虽然LCP取向的改变对免疫刺激作用的影响较弱，但增加构建物中LAA侧链的长度可以增强小鼠模型的抗体反应。此外，用铅LCP构建物免疫的小鼠也能够在五个月的过程中保持抗体活性。这些发现强调了LAA部分在鼻腔多肽疫苗开发中的重要性，并证实了其侧链长度对结构的免疫原性有影响。(C)2016爱思唯尔有限公司。保留所有权利。
Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside a universal T-helper epitope (P25) in four LCP constructs of different spatial orientation or LAA lengths. Through structure-activity studies, it was discovered that while the alteration of the LCP orientation had a weaker effect on immunostimulation, increasing the LAA side chain length within the construct increased antibody responses in murine models. Furthermore, the mice immunised with the lead LCP construct were also able to maintain antibody activity throughout the course of five months. These findings highlight the importance of LAA moieties in the development of intranasal peptide vaccines and confirmed that its side chain length has an effect on the immunogenicity of the structure. (C) 2016 Elsevier Ltd. All rights reserved.