Lipopeptide nanoparticles: development of vaccines against hookworm parasite

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.

Item ID: 40134
Item Type: Article (Research - C1)
ISSN: 1860-7187
Keywords: conformational analysis; hookworm parasite; nanoparticles; peptides; vaccines
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC Program Grant 496600
Date Deposited: 19 Aug 2015 01:02
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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