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Lipopeptide-Based Oral Vaccine Against Hookworm Infection

2019; Oxford University Press; Volume: 221; Issue: 6 Linguagem: Inglês

10.1093/infdis/jiz528

1537-6613

Stacey Bartlett, Ramon M. Eichenberger, Reshma J. Nevagi, Khairunnisa Abdul Ghaffar, Nirmal Marasini, Yang Dai, Alex Loukas, István Tóth, Mariusz Skwarczyński,

Helminth infection and control

Abstract Background The human hookworm, Necator americanus, is a parasite that infects almost half a billion people worldwide. Although treatment is available, vaccination is favorable to combat the spread of this parasite due to its wide distribution and continuous reinfection cycle in endemic communities. Methods We have designed a lipopeptide oral delivery system using a B-cell epitope derived from the aspartic protease Na-APR-1 from N americanus, attached to a T-helper epitope. Lipopeptides were self-assembled into nanoparticles or entrapped in liposomes that were electrostatically coated with alginate and trimethyl chitosan polymer shields. The adjuvant-free vaccine candidates were orally administered to mice and generated a humoral immune response against both peptide antigen, and the parent protein in the hookworm gut. Results The vaccine candidates were evaluated in a rodent hookworm challenge model, resulting in up to 98% and 99% decreases in mean intestinal worm and egg burdens in immunized mice, respectively. Conclusions Lipopeptide survived the gastrointestinal conditions, induced humoral immune responses and drived protection against parasite challenge infection.