Experimental hookworm vaccine shows promising protection in phase 2 human trial

Researchers at the George Washington University School of Medicine and Health Sciences in partnership with Baylor College of Medicine report encouraging results from a phase 2 clinical trial evaluating a candidate vaccine to prevent hookworm infection—one of the world’s most common parasitic diseases. The findings, published in The Lancet Infectious Diseases, show that a formulation of the investigational vaccine significantly reduced the intensity of infection in healthy adult volunteers exposed to the parasite under carefully controlled conditions.

“An effective hookworm vaccine could become an essential tool to prevent anemia and improve health outcomes in vulnerable populations,” said David Diemert, lead researcher and Professor of Medicine at the George Washington University School of Medicine & Health Sciences. “These findings represent an important step toward that goal.”

Hookworm infects an estimated 113 million people globally—some estimates suggest more than 400 million—primarily in sub-Saharan Africa, Southeast Asia, and South America. The parasite feeds on blood in the small intestine and is a major cause of iron-deficiency anemia, particularly in children and pregnant women in low-resource settings. There is currently no licensed vaccine to prevent hookworm disease.

“Almost 40% of children under 5 years of age struggle with anemia, and an effective hookworm vaccine could give many of them the opportunity to live a healthy, productive life,” said Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and co-director of the Texas Children’s Hospital Center for Vaccine Development.

Trial

The trial involved 39 healthy adults in Washington, D.C. Participants received three doses of 1 of 3 vaccine formulations or placebo and then were exposed to the parasite via a Controlled Human Hookworm Infection. All of the vaccine candidates had previously undergone safety testing in phase 1 trials conducted in the United States, Brazil, and Gabon, but they had not been tested against actual infections.

Each candidate contains a protein or “antigen” known as Na-GST-1 that appears capable of generating a strong immune response against hookworm infections. The candidate that was the most effective in the phase 2 trial was formulated with Na-GST-1 in combination with an “adjuvant” called CpG, which is intended to enhance the vaccine’s immune response.

Key findings

• Participants who received the Na-GST 1/Al–CpG vaccine showed a dramatically lower intensity of infection after exposure: maximal hookworm egg count was median 0.0 eggs per gram of feces compared with the placebo group (median 66.7 eggs)
• Peak eosinophil levels—a blood marker linked to parasitic infection—were significantly lower in the Na-GST-1/Al–CpG group of participants.
• This group of participants also produced the highest levels of anti–Na-GST-1 antibodies, suggesting these antibodies may help protect against infection.

Based on these results, the Na‑GST‑1/Al–CpG formulation has been selected to be advanced for further clinical evaluation as a standalone or possibly as a combination vaccine.

“A combination vaccine could pack a particularly powerful punch because, in areas with high rates of both malaria and hookworm, it’s not always clear which one is the primary cause of anemia,” said Maria Elena Bottazzi, senior associate dean of the National School of Tropical Medicine at Baylor College of Medicine and co-director of the Texas Children’s Hospital Center for Vaccine Development.