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Human Hookworm Vaccines that Interrupt Blood-feeding<br />

Loukas, A. (1), M. Pearson (2), N. Ranjit (1), D. Pickering (1), J. Bethony (2), M.E. Bottazzi<br />

(2) & P. Hotez (2,3)<br />

(1) Queensland Institute of Medical Research, Brisbane, Australia; (2) George Washington University,<br />

Washington DC, USA; (3) Sabin Vaccine Institute, Washington DC, USA<br />

Hookworms are gastrointestinal nematodes that infect almost one billion people in<br />

developing countries. The main clinical symptom of human hookworm infections is irondeficiency<br />

anemia, as a direct consequence of the intestinal blood loss resulting from the<br />

parasite’s feeding behaviour. Although treatment is available and currently used for the<br />

periodic removal of adult hookworms from patients, this approach has not effectively<br />

controlled hookworm in areas of rural poverty. Moreover, treated individuals remain<br />

susceptible to reinfection following exposure to third-stage infective hookworm larvae (L3)<br />

in the soil as early as 4-12 months following drug treatment. Therefore, a prophylactic<br />

vaccine against hookworm infection would provide an attractive additional tool for the public<br />

health control of this disease. The feasibility of developing a vaccine is based on the prior<br />

success of an attenuated larval vaccine against canine hookworm. Several laboratory and<br />

field studies have explored the development of a human anti-hookworm vaccine, describing<br />

potential protective mechanisms and identifying candidate antigens, one of which is now in<br />

clinical trials. Antigen discovery has focused on two distinct developmental stages of the<br />

parasite – (1) secreted proteins from the infective third stage larva (L3) and (2) intestinal<br />

proteases that digest haemoglobin from the adult worm. This presentation will focus on the<br />

biology of the blood-feeding process, and the selection and testing in pre-clinical efficacy<br />

studies of the major enzymes involved in the haemoglobin digestion pathway.<br />

5 th International Congress of Nematology, 2008 42

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