The use of a conformational cathepsin D-derived epitope for vaccine development against Schistosoma mansoni

被引:16
作者
Fuaad, Abdullah A. H. Ahmad [1 ]
Roubille, Romain [1 ]
Pearson, Mark S. [2 ]
Pickering, Darren A. [2 ]
Loukas, Alex C. [2 ]
Skwarczynski, Mariusz [1 ]
Toth, Istvan [1 ,3 ]
机构
[1] Univ Queensland St Lucia, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia
[2] James Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld 4878, Australia
[3] Univ Queensland St Lucia, Sch Pharm, Woolloongabba, Qld 4012, Australia
基金
英国医学研究理事会;
关键词
Nanoparticles; Subunit peptide-based vaccine; Lipid core peptide; Epitope modification; Peptide conformation; Self-assembly; Schistosomiasis; Schistosoma mansoni; PROTEIN SECONDARY STRUCTURE; T-CELL; PEPTIDE; LIPOPEPTIDE; CANDIDATES; SYSTEM;
D O I
10.1016/j.bmc.2015.01.033
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Schistosomiasis is caused by the infection from Schistosoma species. Among these, Schistosoma mansoni is one of the major species that infects millions of people worldwide. The use of praziquantel is effective in clearing the infestation but treatment of a large and widespread population in endemic areas is unsustainable. Thus, synergistic approach of using drug and vaccination can serve as an alternative to the current treatment. In this study, we have developed vaccine candidates that composed of three components: a B-cell epitope derived from S. mansoni cathepsin D protein (Sm-CatD) flanked by GCN4 helix promoting peptide; a promiscuous T-helper epitope (P25); and a lipid core peptide system, in attempt to develop self-adjuvanting vaccine candidates against the schistosome. Physicochemical properties of the vaccine candidates were analysed and antibodies to each construct were raised in BALB/c mice. The vaccine candidates were able to self-assemble into particles that induced high titres of IgG without the use of additional adjuvant. The antibody levels were comparable to that induced by peptide formulated with strong but toxic Freund's adjuvant. The integration of a GCN4 sequence induced the helical conformation of the epitope, while the addition of the T helper peptide was very effective in inducing consistent IgG-specific antibodies response amongst mice. These findings are particularly encouraging for the development of efficient and immunogenic vaccine against schistosomiasis. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1307 / 1312
页数:6
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