From 2000 to 2017 the Sabin Vaccine Institute partnered with the Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine in Houston, Texas to develop safe, effective and low-cost vaccines for infectious and neglected tropical diseases. Baylor College of Medicine and Texas Children’s Hospital Center for Vaccine Development continue this research as of May 2017.
Through a network of global partners, the Sabin Vaccine Institute Product Development Partnership (Sabin PDP) spearheaded the development of the first and only preventative vaccine for human hookworm disease. The Sabin PDP originally launched as the Human Hookworm Vaccine Initiative in 2000. As of May 2017, Baylor College of Medicine and the Texas Children’s Hospital’s Center for Vaccine Development continue this research.
The Human Hookworm Vaccine is a bivalent vaccine for the prevention of moderate to heavy hookworm infection due to N. americanus, the hookworm species most commonly infecting humans. The vaccine is intended primarily for pre-school and school-age children living in Latin America and the Caribbean, sub-Saharan Africa and Southeast Asia, where N. americanus is endemic. Children are at greatest risk for experiencing severe growth, developmental and cognitive impairments as a result of hookworm-induced anemia, and they suffer the greatest morbidity compared to any other age group.
The recombinant protein-based product comprises two N. americanus antigens, Na-Glutathione S-Transferase-1 (Na-GST-1) and Na-Aspartic Protease-1 (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 aim of the vaccine is to induce neutralizing antibodies that will reduce host blood loss and the number of hookworms attached to the gut. Preclinical studies have shown proof of concept of protection when each antigen is used as a vaccine.
Phase I clinical trials for the Na-GST-1 and Na-APR-1 hookworm vaccines advance in the United States, Brazil and Gabon, with the ultimate aim of co-formulation into a single vaccine.
The initiative has been supported by the Bill & Melinda Gates Foundation, Dutch Ministry of Foreign Affairs, European Commission Framework Programme 7, Government of Brazil and the Michelson Medical Research Foundation.
Hookworm is an intestinal parasite most commonly found in tropical and subtropical climates worldwide, particularly in sub-Saharan Africa, Latin America and Southeast Asia. It is estimated to infect more than 400 million people, most of whom live in extreme poverty. Hookworm larvae are present in the fecal material of infected individuals, which can then spread in areas of poor sanitation or where “night soil” is used as fertilizer. Children and those walking barefoot are most susceptible. Hookworms are half-inch long worms (or helminths) that attach themselves to the intestinal wall of their human host and feed on blood. Left untreated, hookworm causes intestinal blood loss leading to iron deficiency anemia and protein malnutrition, particularly in pregnant women and children.
One-quarter to one-third of all pregnant women in Africa are infected with hookworm. These women are at risk for increased maternal morbidity and mortality and fetal loss or prematurity due to severe anemia and protein malnutrition. Chronic hookworm infection in children can also result in anemia and malnutrition and contributes to physical and intellectual impairment, learning difficulties and poor school performance.
In addition to its impact on global health, hookworm infection is also a major cause of poverty because of its long-term and chronic effects on childhood development and worker productivity. By some estimates, chronic hookworm infection in childhood reduces future wage earnings by up to 40 percent.
Hookworm is one of three major soil-transmitted helminth infections that, together, are the most important neglected tropical diseases in terms of disability-adjusted life years (DALYs). The recent Global Burden of Disease Study (GBD) 2015 estimated that hookworm alone leads to the loss of 1.8 million DALYs annually.
Why We Need a Vaccine
Despite highly commendable efforts worldwide to make donated drugs available to everyone at risk, only about half of the children who require deworming treatment are receiving the medication they need. Further, the GBD 2013 report estimates that since 1990, NTD treatment programs have resulted in substantial reductions in the prevalence of a number of NTDs including lymphatic filariasis, trachoma, onchocerciasis and ascariasis; however, the prevalence of hookworm infection has decreased by only 5 percent in the same period. An effective vaccine is needed to control hookworm infection due to the rapid rates of post-treatment re-infection, the inadequate efficacy of anthelmintic drugs when administered as a single dose, as well as the potential of drug resistance for current anthelmintic therapy.
The project is focused on developing and testing a vaccine to prevent moderate to severe hookworm infection in children living in endemic areas. The goal is to reduce the anemia, delayed physical growth and impaired cognitive development caused by hookworm infection. The first dose of the vaccine may be co-administered with a single dose of an anthelminthic drug, such as albendazole. The minimum acceptable efficacy of the vaccine is 80% against moderate and heavy hookworm infections, with duration of protection of at least five years.