Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine

Dougall, Annette M., Skwarczynski, Mariusz, Khoshnejad, Makan, Chandrudu, Saranya, Daly, Norelle L., Toth, Istvan and Loukas, Alex (2014) Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine. Human Vaccines and Immunotherapeutics, 10 2: 399-409. doi:10.4161/hv.27057

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Author Dougall, Annette M.
Skwarczynski, Mariusz
Khoshnejad, Makan
Chandrudu, Saranya
Daly, Norelle L.
Toth, Istvan
Loukas, Alex
Title Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine
Formatted title
Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine
Journal name Human Vaccines and Immunotherapeutics   Check publisher's open access policy
ISSN 2164-554X
2164-5515
Publication date 2014
Year available 2013
Sub-type Article (original research)
DOI 10.4161/hv.27057
Open Access Status
Volume 10
Issue 2
Start page 399
End page 409
Total pages 11
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Collection year 2014
Language eng
Formatted abstract
The self-adjuvanting lipid core peptide (LCP) system offers a safe alternative vaccine delivery strategy, eliminating the need for additional adjuvants such as CpG Alum. In this study, we adopted the LCP as a scaffold for an epitope located on the surface of the cathepsin D hemoglobinase (Sm-CatD) of the human blood fluke Schistosoma mansoni. Sm-CatD plays a pivotal role in digestion of the fluke's bloodmeal and has been shown to be efficacious as a subunit vaccine in a murine model of human schistosomiasis. Using molecular modeling we showed that S. mansoni cathepsin D possesses a predicted surface exposed a-helix (A263K) that corresponds to an immunodominant helix and target of enzyme-neutralizing antibodies against Necator americanus APR-1 (Na-APR-1), the orthologous protease and vaccine antigen from blood-feeding hookworms. The A263K epitope was engineered as two peptide variants, one of which was flanked at both termini with a coil maintaining sequence, thereby promoting the helical characteristics of the native A263K epitope. Some of the peptides were fused to a self-adjuvanting lipid core scaffold to generate LCPs. Mice were vaccinated with unadjuvanted peptides, peptides formulated with Freund's adjuvants, or LCPs. Antibodies generated to LCPs recognized native Sm-CatD within a soluble adult schistosome extract, and almost completely abolished its enzymatic activity in vitro. Using immunohistochemistry we showed that anti-LCP antibodies bound to the native Sm-CatD protein in the esophagus and anterior regions of the gastrodermis of adult flukes. Vaccines offer an alternative control strategy in the fight against schistosomiasis, and further development of LCPs containing multiple epitopes from this and other vaccine antigens should become a research priority. 
Keyword Cathepsin D
Conformational epitope
Lipopeptide
Peptide antigen
Schistosomiasis
Self-adjuvanting
Vaccine delivery
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
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