Simerska Pavla, Suksamran Tittaya, Ziora Zyta Maria, Rivera Fabian de Labastida, Engwerda Christian, Toth Istvan
School of Chemistry and Molecular Biosciences, The University of Queensland, Cooper Road, St. Lucia 4072, Queensland, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, Cooper Road, St. Lucia 4072, Queensland, Australia.
Vaccine. 2014 Aug 20;32(37):4743-50. doi: 10.1016/j.vaccine.2014.06.049. Epub 2014 Jun 23.
The lipid core peptide (LCP) system has successfully been used in development of peptide-based vaccines against cancer and infectious diseases (such as group A streptococcal infection). CD8(+) T cells are important targets for vaccines, however developing a vaccine that activates long-lasting immunity has proven challenging. The ability of LCP vaccines to activate antigen-specific CD8(+) and/or CD4(+) T cell responses was tested using compounds that contained two or four copies of OVA257-264 and/or OVA323-339 peptides conjugated to LCP, which are recognised by OTI (CD8(+) specific) and OTII (CD4(+) specific) T cells, respectively. The LCP-ovalbumin vaccines developed in this study were synthesised in 30% yields and showed no significant haemolytic effect on red blood cells (below 4% haemolysis when tested with compounds at up to 100μM concentrations). Promising in vivo data in mice suggested that this LCP-ovalbumin vaccine system could act as a novel and potent vehicle for the stimulation of robust antigen-specific CD8(+) T cell responses.
脂质核心肽(LCP)系统已成功应用于开发针对癌症和传染病(如A组链球菌感染)的肽基疫苗。CD8(+) T细胞是疫苗的重要靶点,然而,开发一种能激活持久免疫的疫苗已被证明具有挑战性。使用与LCP偶联的含有两个或四个OVA257-264和/或OVA323-339肽拷贝的化合物测试了LCP疫苗激活抗原特异性CD8(+)和/或CD4(+) T细胞反应的能力,这些肽分别被OTI(CD8(+)特异性)和OTII(CD4(+)特异性)T细胞识别。本研究中开发的LCP-卵清蛋白疫苗的合成产率为30%,并且对红细胞没有显著的溶血作用(当用浓度高达100μM的化合物测试时,溶血率低于4%)。小鼠体内的有前景的数据表明,这种LCP-卵清蛋白疫苗系统可以作为一种新型且有效的载体,用于刺激强大的抗原特异性CD8(+) T细胞反应。