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Engineered Antigen Shows Promise Against Hookworm Disease in Clinical Trial

Healthcare worker preparing a vaccine injection with syringe and vial in gloved hands.
Credit: Nappy / Unsplash.
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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.”


Reference: DiRosato CK, Malkin EM, Lee SM, et al. Na-GST-1 adsorbed on Alhydrogel co-administered with different Toll-like receptor agonists in hookworm-naive adults using a controlled human infection model in the USA: a phase 2, double-blind, randomised controlled trial. Lancet Infect Dis. 2026. doi: 10.1016/S1473-3099(26)00018-6

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