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

Ahmad Fuaad, Abdullah A.H., Roubille, Romain, Pearson, Mark S., Pickering, Darren A., Loukas, Alex C., Skwarczynski, Mariusz, and Toth, Istvan (2015) The use of a conformational cathepsin D-derived epitope for vaccine development against Schistosoma mansoni. Bioorganic & Medicinal Chemistry, 23. pp. 1307-1312.

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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 unsus-tainable. Thus, synergistic approach of using drug and vaccination can serve as an alternative to the cur-rent 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 can-didates were able to self-assemble into particles that induced high titres of IgG without the use of addi-tional 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.

Item ID: 39214
Item Type: Article (Research - C1)
ISSN: 1464-3391
Keywords: nanoparticles; subunit peptide-based vaccine; lipid core peptide; epitope modification; peptide conformation; self-assembly; Schistosomiasis; Schistosoma mansoni
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC Program Grant 496600
Date Deposited: 18 Jun 2015 03:25
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 50%
03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030406 Proteins and Peptides @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920412 Preventive Medicine @ 50%
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