Lipopeptide Nanoparticles: Development of Vaccines against Hookworm Parasite

被引：24

作者：

Fuaad, Abdullah A. H. Ahmad ^{[1
]}

Pearson, Mark S. ^{[2
]}

Pickering, Darren A. ^{[2
]}

Becker, Luke ^{[2
]}

Zhao, Guangzu ^{[1
]}

Loukas, Alex C. ^{[2
]}

Skwarczynski, Mariusz ^{[1
]}

Toth, Istvan ^{[1
,3
]}

机构：

[1] Univ Queensland St Lucia, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia

[2] James Cook Univ, Queensland Trop Hlth Alliance Lab, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld 4870, Australia

[3] Univ Queensland St Lucia, Sch Pharm, Woolloongabba, Qld 4012, Australia

来源：

CHEMMEDCHEM | 2015年 / 10卷 / 10期

基金：

英国医学研究理事会;

关键词：

conformational analysis; hookworm parasite; nanoparticles; peptides; vaccines; GROUP-A STREPTOCOCCUS; SECONDARY STRUCTURE PREDICTION; SELF-ADJUVANTING VACCINE; CORE-PEPTIDE SYSTEM; M-PROTEIN; NEUTRALIZING ANTIBODIES; MULTIVALENT VACCINE; SCHISTOSOMA-MANSONI; RECEPTOR; INFECTION;

D O I：

10.1002/cmdc.201500227

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 beta-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.

引用

页码：1647 / 1654

页数：8

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