Fuaad, Abdullah A.H. Ahmad, Pearson, Mark S., Pickering, Darren A., Becker, Luke, Zhao, Guangzho, Loukas, Alex C., Skwarczynski, Mariusz, and Toth, Istvan (2015) Lipopeptide nanoparticles: development of vaccines against hookworm parasite. ChemMedChem, 10 (10). pp. 1647-1654.

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Abstract

Necator americanus (hookworm) infects over half a billion people worldwide. Anthelminthic drugs are commonly used to treat the infection; however, vaccination is a more favorable strategy to combat this parasite. We designed new B-cell peptide epitopes based on the aspartic protease of N. americanus (Na-APR-1). The peptides were conjugated to self-adjuvanting lipid core peptide (LCP) systems via stepwise solid-phase peptide synthesis (SPPS) and copper catalyst azide–alkyne cycloaddition (CuAAC) reactions. The LCP vaccine candidates were able to self-assemble into nanoparticles, were administered to mice without the use of additional adjuvant, and generated antibodies that recognized the parent epitope. However, only one LCP derivative was able to produce a high titer of antibodies specific to Na-APR-1; circular dichroism analyses of this compound showed a β-sheet conformation for the incorporated epitope. This study provides important insight in epitope and delivery system design for the development of a vaccine against hookworm infections.

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