Experimental Hookworm Vaccine Trial Shows Promise

Researchers at the George Washington University School of Medicine and Health Sciences (SMHS), 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 Tuesday 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 SMHS. "These findings represent an important step toward that goal."

Hookworm infects hundreds of millions people globally-some estimatessuggest 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% percent of children under five 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 (NSTM) at Baylor and co-director of the Texas Children's Hospital Center for Vaccine Development (CVD).

The trial involved 39 healthy adults in Washington, D.C. Participants received three doses of one of three vaccine formulations or placebo and were then 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 had not been tested against actual infections. The trial was funded by the National Institute of Allergy and Infectious Diseases.

Each candidate vaccine contains a protein or antigencalled Na-GST-1 that appears capable of generating a strong immune response against hookworm infections. The most effective candidate in the Phase 2 trial was formulated with Na-GST-1 in combination with an adjuvant-an ingredient intended to enhance immune response-called CpG.

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 NSTM and co-director of Texas Children's Hospital CVD.

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