Hookworms (including Necator americanus) infect more people than HIV and malaria combined, predominantly in third world countries. Treatment of the infection with chemotherapy has limited efficacy and re-infections after treatment are common. The development of vaccines for these infections could substantially reduce the global disability associated with these parasites.
Hookworm hemoglobin digestion cascade protease Na-APR-1, crucial for pathogens feeding, was chosen as antigens for vaccine design. However, high-yield production of these eukaryotic proteins was problematic, and it induced mainly redundant immune responses. Thus, appropriate B-cell epitopes have been identified and conjugated to self-adjuvanting delivery systems using SPPS or click reactions [1,2]. Produced conjugates were formulated into nanoparticles under aqueous conditions. Several series of vaccine candidates were tested in mice model. The lead candidates induced robust neutralizing humoral immune responses which strongly depended on conformational properties of the peptide epitopes incorporated into conjugates. The use of potentially toxic adjuvants was eliminated, and vaccine candidates showed generally good safety profile. The adjuvant-free peptide-based vaccine candidates were orally administered to mice and generated humoral immune responses against peptide antigen, and the parent protein in the hookworm gut. The vaccine candidates were evaluated in a rodent hookworm challenge model, resulting in elimination of intestinal worm and egg burdens in immunized mice. Our self-adjuvanting approach showed promise as a technically straightforward and potentially safe oral hookworm vaccine.