Lipopeptide Nanoparticles: Development of Vaccines against Hookworm Parasite

ChemMedChem. 2015 Oct;10(10):1647-54. doi: 10.1002/cmdc.201500227. Epub 2015 Aug 12.

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.

Keywords: conformational analysis; hookworm parasite; nanoparticles; peptides; vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Helminth / immunology
  • Aspartic Acid Proteases / chemistry
  • Aspartic Acid Proteases / immunology*
  • Female
  • Hookworm Infections / immunology
  • Hookworm Infections / parasitology*
  • Lipopeptides / chemistry
  • Lipopeptides / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Conformation
  • Nanoparticles / chemistry*
  • Necator americanus / enzymology
  • Necator americanus / immunology*
  • Particle Size
  • Structure-Activity Relationship
  • Vaccines, Synthetic / chemistry*
  • Vaccines, Synthetic / immunology*

Substances

  • Antibodies, Helminth
  • Lipopeptides
  • Vaccines, Synthetic
  • Aspartic Acid Proteases