The Human Hookworm Vaccine

Abstract

Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases.

Fig. 1

Benefit of adding an effective Human Hookworm Vaccine to Mass Drug Administration (MDA) in order to achieve hookworm elimination, using an economic dynamic transmission compartment model with compartments representing human and free-living hookworm populations. In this scenario, albendazole is administered annually to 75% of children ages 1–14 and the MDA + vaccination (2 doses) is administered to the same group once every 5 years (assuming a 5-year duration of vaccine protection). Albendazole cure rate = 78.4%; vaccine efficacy = 70%; mean baseline worm burden = 30 (adults), 15 (children). Top: MDA alone. Bottom: MDA + vaccination.

Fig. 2

Benefit of an effective Human Hookworm Vaccine in reducing disease burden, as measured by disability adjusted life years (DALYs), relative to MDA alone. Only disability resulting from anemia is included in this analysis. Albendazole cure rate = 78.4%; vaccine efficacy = 70%; mean baseline worm burden = 30 (adults), 15 (children).