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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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Ahmad Fuaad AA,Roubille R,Pearson MS,Pickering DA,Loukas AC,Skwarczynski M,Toth I

doi

10.1016/j.bmc.2015.01.033

subject

Has Abstract

pub_date

2015-03-15 00:00:00

pages

1307-12

issue

6

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)00049-8

journal_volume

23

pub_type

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