Lipopeptide-Based Oral Vaccine Against Hookworm Infection

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.

Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein

“…The high PDI generated in this study is associated with self-assembly into rod-like particles, which are 110 nm in diameter for VC-1 , and around 130 nm in diameter for VC-2 . The particle size and shape observed is similar to the rod-like and worm-like particles previously reported for self-assembled lipidated constructs [ 32 , 48 ]. Particle aggregations were also observed in the TEM images ( Figure S9, Supporting Information ).…”

Polyacrylate–Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus

“…In contrast, despite inducing similar IgG titers following boost immunization, PMA-P-J8 + CTB was not able to trigger the production of highly opsonic antibodies. Notably, PMA-P-J8 induced strong oral immune responses against a weak peptide antigen after a single dose (30 μg), while other oral delivery systems for peptide antigens have required multiple doses, and hundreds of micrograms in total [61].…”

Rodent Models for the Study of Soil-Transmitted Helminths: A Proteomics Approach

“…Different studies have used the N. brasiliensis rodent model to (i) discover new vaccine candidates that could be extrapolated to human hookworm infections and (ii) develop novel administration routes of known vaccine candidates to improve their immunogenicity and reduce undesirable effects. Indeed, since N. brasiliensis has a highly conserved orthologue of Na-APR-1 (Bartlett et al, 2020), Bartlet et al designed a lipopeptidebased vaccine using a B cell epitope derived from Na-APR-1, attached to a T helper epitope and administered it orally. In this study, several lipidated peptides were obtained and tested for vaccine efficacy using the N. brasiliensis hookworm model (Bartlett et al, 2020).…”