Intranasal Delivery of Liposomes-Based Lipopeptide Hookworm Vaccine Diminished its Ability to Protect Mice Against Hookworm Challenge

Abstract

Background Hookworm infection is particularly problematic for middle- to low-income countries. While treatment methods are currently available, vaccination may be the ideal intervention, as it could offer cost-effective long-term protection against infection and reinfection. Methods Previously established lipopeptide-based vaccine formulations, proven to be effective in an oral application, were adapted for an intranasal administration using a predicted B-cell peptide epitope derived from the hookworm Necator americanus aspartic protease-1 (Na-APR-1) protein and a universal T-helper epitope attached to two lipid moieties, Pam2Cys or lipid core peptide (LCP). The lipopeptides were encapsulated into liposomes or self-assembled into nanoparticles. The intranasal vaccine candidates were evaluated in a rodent hookworm challenge model. Results The vaccine candidates were formulated to optimal sizes and charges for uptake by immune cells. However, no significant serum antibody response was elicited, and no protection was demonstrated following hookworm challenge. Conclusion In contrast to the previously reported effective oral immunization, intranasal delivery of lipopeptide-based vaccine failed to trigger significant antibody responses in mice against hookworm and had no effect on parasite numbers following challenge infection.