Abstract
BackgroundHookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1.Methods and FindingsWe show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056) and fecal egg counts (p = 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood.ConclusionTo the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine.
Highlights
Hookworms infect more than 700 million people in tropical and subtropical regions of the world
The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1
We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p 1⁄4 0.056) and fecal egg counts (p 1⁄4 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum
Summary
Hookworms infect more than 700 million people in tropical and subtropical regions of the world. Canines can be successfully vaccinated against infection with the dog hookworm, Ancylostoma caninum, by immunization with third-stage infective larvae (L3) that have been attenuated with ionizing radiation [5,6,7]. Varying levels of vaccine efficacy have been reported for the major antigens secreted by hookworm L3 using hamsters [8,9] and dogs [10]. We suggest that an ideal hookworm vaccine would require a cocktail of two recombinant proteins, one targeting the infective larva and the second targeting the blood-feeding adult stage of the parasite [11]. Hookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. The aim is to find a vaccine that works against more than one of the stages that the parasite passes through in its lifecycle
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