The Use of Microwave-Assisted Solid-Phase Peptide Synthesis and Click Chemistry for the Synthesis of Vaccine Candidates Against Hookworm Infection.

A protein-based vaccine approach against hookworm infection has failed to deliver the expected outcome, due to a problem with an allergic response in the patient or difficulties in the proteins' production. This implication could be overcome by using a chemically synthesized peptide-based vaccine approach. This approach utilizes minimal pathogenic components that are necessary for the stimulation of the immune response without triggering adverse side effects. To boost the peptide's immunogenicity, a lipid core peptide (LCP) system can be utilized as a carrier molecule/immunostimulant. This chapter describes in detail the synthesizing of protected lipoamino acid, the self-adjuvanting moiety (LCP core), the peptide epitope, and the final vaccine candidate. The subunit peptide and the LCP core were synthesized using microwave-assisted solid-phase peptide synthesis (SPPS). Then the final hookworm vaccine construct was assembled using the copper-catalyzed azide-alkyne cycloaddition, or "click," reaction.

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 ß-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.