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.