A phase 2 human clinical trial of an antigen for a parasitic infection caused by hookworms has been shown to be effective in limiting the intensity of infection, paving the way for the development of a vaccine.
A team of international scientists from The George Washington University, the University of Nottingham and Baylor College of Medicine have worked together over many years to find treatment for disease caused by hookworms. They identified Necator americanus Glutathione S-transferase-1 (Na-GST-1) as a critical enzymatic step in hookworm blood feeding and as a leading target for vaccine development.
Using the Na-GST-1 antigen the team developed a controlled human hookworm infection (CHHI) model to evaluate the impact of candidate hookworm vaccines on infection. The results from the 39 participants who volunteered in the trial showed a reduction in the intensity of infection and have been published today in The Lancet Infectious Diseases.
The hookworm Necator americanus is found in tropical climates and gets into the body through the skin, usually when trodden on barefoot. The worm then sheds its own skin, which is thought to trigger a diversionary immune response. If left untreated heavy infections result in anaemia and long-term discomfort and disability.
Apart from malaria, hookworm is one of the most important parasitic infections in terms of global burden of disease. An estimated 113 million people are infected worldwide, with the largest concentration of cases on the African continent and Southeast Asia although some estimates suggest that the actual number of people infected is more than 400 million.
Na-GST-1 is a lead candidate vaccine antigen that scientists have long thought would induce neutralizing antibodies against the native enzyme, which performs an essential function in the adult hookworm's host blood digestion pathway. Vaccination with Na-GST-1 aims to prevent worm development or cause parasite death, both of which would result in reduced disease manifestations and interrupt transmission.
Professor David Diemert, from George Washington University led the trial, he said: "This study is an important step in developing an effective hookworm vaccine, which would become an essential tool to prevent anaemia and improve health outcomes in vulnerable populations."
David Pritchard, Emeritus Professor of Parasite Immunology, from the University of Nottingham's School of Pharmacy has led this project in the UK and in 2006 he allowed 50 hookworms to burrow into his arm to test the effect these parasites have on humans. This work established the necessary safety and regulatory criteria to allow this human infection study to take place.
This new study is a significant step towards developing an effective vaccine for hookworm disease, something myself and colleagues have been working towards for over 40 years. In the 1980s, our research group started investigating the immunology of necatoriasis (Necator americanus/hookworm disease). In particular, we were interested in explaining why hookworm infections accumulated throughout life in the tropics and returned so quickly after effective worm expulsion chemotherapy. Fast forward to 2026 and we've now shown that glutathione-S-transferase vaccinates against infection in human challenge studies using a PNG isolate of Necator americanus.
