Lipopeptide Nanoparticles: Development of Vaccines against Hookworm Parasite.
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.
School of Chemistry and Molecular Biosciences, The University of Queensland (St. Lucia), Brisbane, Queensland 4072 (Australia).
Abdullah A H Ahmad
AA
Fuaad
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland 4870 (Australia).
Mark S
MS
Pearson
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland 4870 (Australia).
Darren A
DA
Pickering
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland 4870 (Australia).
Luke
L
Becker
School of Chemistry and Molecular Biosciences, The University of Queensland (St. Lucia), Brisbane, Queensland 4072 (Australia).
Guangzu
G
Zhao
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland 4870 (Australia).
Alex C
AC
Loukas
School of Chemistry and Molecular Biosciences, The University of Queensland (St. Lucia), Brisbane, Queensland 4072 (Australia). m.skwarczynski@uq.edu.au.
Mariusz
M
Skwarczynski
School of Chemistry and Molecular Biosciences, The University of Queensland (St. Lucia), Brisbane, Queensland 4072 (Australia).|School of Pharmacy, The University of Queensland (St Lucia), Woolloongabba, Queensland 4012 (Australia).
Istvan
I
Toth
D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D057055:Aspartic Acid Proteases / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006725:Hookworm Infections / Q000276:immunology / Q000469:parasitology*; D055666:Lipopeptides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D017221:Necator americanus / Q000201:enzymology / Q000276:immunology*; D010316:Particle Size; D013329:Structure-Activity Relationship; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology*
D000909:Antibodies, Helminth; D055666:Lipopeptides; D014614:Vaccines, Synthetic; D057055:Aspartic Acid Proteases
conformational analysis; hookworm parasite; nanoparticles; peptides; vaccines