title: The use of a conformational cathepsin D-derived epitope for vaccine development against Schistosoma mansoni.
abstract: 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.
authors: School of Chemistry and Molecular Biosciences, The University of Queensland (St Lucia), Chemistry Blg #68, St Lucia, Brisbane, Queensland 4072, Australia.
authors: Abdullah A H
authors: AA
authors: Ahmad Fuaad
authors: School of Chemistry and Molecular Biosciences, The University of Queensland (St Lucia), Chemistry Blg #68, St Lucia, Brisbane, Queensland 4072, Australia.
authors: Romain
authors: R
authors: Roubille
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia.
authors: Mark S
authors: MS
authors: Pearson
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia.
authors: Darren A
authors: DA
authors: Pickering
authors: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland 4878, Australia.
authors: Alex C
authors: AC
authors: Loukas
authors: School of Chemistry and Molecular Biosciences, The University of Queensland (St Lucia), Chemistry Blg #68, St Lucia, Brisbane, Queensland 4072, Australia.
authors: Mariusz
authors: M
authors: Skwarczynski
authors: School of Chemistry and Molecular Biosciences, The University of Queensland (St Lucia), Chemistry Blg #68, St Lucia, Brisbane, Queensland 4072, Australia; School of Pharmacy, The University of Queensland (St Lucia), Woolloongabba, Queensland 4012, Australia. Electronic address: i.toth@uq.edu.au.
authors: Istvan
authors: I
authors: Toth
mesh_terms: D000818:Animals; D002402:Cathepsin D / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D015394:Molecular Structure; D012550:Schistosoma mansoni / Q000276:immunology*; D012552:Schistosomiasis / Q000276:immunology / Q000517:prevention & control; D013329:Structure-Activity Relationship; D014612:Vaccines / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D000939:Epitopes; D014612:Vaccines; D002402:Cathepsin D
keywords: Epitope modification; Lipid core peptide; Nanoparticles; Peptide conformation; Schistosoma mansoni; Schistosomiasis; Self-assembly; Subunit peptide-based vaccine