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.

The use of a conformational cathepsin D-derived epitope for vaccine development against Schistosoma mansoni.

Schistosomiasis is caused by the infection from Schistosoma species. Among these, Schistosoma mansoni is one of the major species that infects millions of people worldwide. The use of praziquantel is effective in clearing the infestation but treatment of a large and widespread population in endemic areas is unsustainable. Thus, synergistic approach of using drug and vaccination can serve as an alternative to the current treatment. In this study, we have developed vaccine candidates that composed of three components: a B-cell epitope derived from S. mansoni cathepsin D protein (Sm-CatD) flanked by GCN4 helix promoting peptide; a promiscuous T-helper epitope (P25); and a lipid core peptide system, in attempt to develop self-adjuvanting vaccine candidates against the schistosome. Physicochemical properties of the vaccine candidates were analysed and antibodies to each construct were raised in BALB/c mice. The vaccine candidates were able to self-assemble into particles that induced high titres of IgG without the use of additional adjuvant. The antibody levels were comparable to that induced by peptide formulated with strong but toxic Freund's adjuvant. The integration of a GCN4 sequence induced the helical conformation of the epitope, while the addition of the T helper peptide was very effective in inducing consistent IgG-specific antibodies response amongst mice. These findings are particularly encouraging for the development of efficient and immunogenic vaccine against schistosomiasis.