The Hookvac project is conducting clinical trials and advancing the manufacture of the world’s first vaccine to control and prevent hookworm disease in humans. This chronic condition affects lives and livelihoods around the world, mainly in sub-Saharan Africa, south-east Asia and Latin America.

“Hookvac is conducting clinical studies in endemic areas in Africa,” says Remko van Leeuwen, who coordinates the project on behalf of the Amsterdam Institute for Global Health and Development at the Academic Medical Center/University of Amsterdam.

The project is thus paving the way for larger-scale clinical trials and development into a licensed product. “We are also looking into ways of scaling up the production of the required antigens,” van Leeuwen adds.

Better protection from hookworm infection and disease could help to lift the fortunes of entire communities. In some parts of the world, up to a third of the inhabitants are affected by these parasitic worms, which feast on their blood and also lay claim to some of their protein intake.

Common symptoms include gastrointestinal symptoms and iron deficiency anaemia, while advanced disease causes severe malnutrition. As many as 400 million people are thought to be infected. The most vulnerable populations are pregnant women – whose lives and those of unborn babies are at risk – and children, for whom the disease can translate into developmental problems with life-long consequences.

“Hookworm disease is associated with poverty,” says van Leeuwen. Poorer populations are more likely to be affected, and the implications for their health are one of the factors that limit their prospects.

Bye bye bloodsuckers

The larvae lurk in the soil in areas with inadequate sanitation, biding their time until they can pierce someone’s skin. They bore into the feet of barefoot passers-by, or into the hands of farmers working the ground. Eventually, they make their way into the bowel, where they grow into adult worms. 

In areas where this neglected tropical disease is rife, it is typically treated by giving entire groups of people medication to rid them of the worms. Despite its merits, this method has limitations. The drugs don’t always work, they don’t confer any kind of lasting protection, and reinfection is frequent.  

The proposed vaccine is based on two antigens specific to the adult gut hookworm. Antigens are substances that cause the body’s immune system to respond and form antibodies. “We target two enzymes within the hookworm that are essential for its metabolism,” says van Leeuwen. “If you destroy those enzymes, you kill the hookworm.”

While the vaccine may not work for everyone, van Leeuwen is confident that it will enable large numbers of people to develop immunity for several years. “We don’t see it as a one-step solution, but as part of a comprehensive strategy,” he explains. Combining it with the current deworming campaigns could help to stamp out the disease.

Mobilisation for inoculation

Despite its prevalence, hookworm disease has not been a priority for pharmaceutical development. Van Leeuwen attributes this lack of industry interest to the limited scope for return on the substantial investment required. “It’s also a very difficult vaccine to make,” he adds.

The first stages of the vaccine’s development were supported by the Bill & Melinda Gates Foundation and the Dutch Ministry of Foreign Affairs. The current, EU-funded project represents the next step on the long road towards a licensed product. By the time Hookvac ends in 2017, the partners intend to confirm initial findings that the vaccine is safe and able to raise an immune response.

And then, more support will be needed to conduct the remaining clinical trials and complete the development process. The partners are already engaging with funding organisations that might help to make human hookworm history.