Researchers from GW and Baylor College of Medicine published findings earlier this month demonstrating promising results in a clinical trial for an experimental hookworm vaccine, which paves the way for future clinical testing.
The study, which the researchers published March 17 in The Lancet Infectious Diseases, exposed 39 healthy D.C. participants to the hookworm parasite after giving them different versions of a vaccine or placebo and found those given the vaccine experienced lower-intensity infections and developed antibodies to fight the parasite. Five researchers said the results represent the latest milestone in a nearly 25-year effort to develop a vaccine against hookworm — one of the most common parasites in developing countries.
David Diemert, the study’s lead researcher and GW professor of medicine and microbiology, immunobiology and tropical medicine, said while it will be harder to get funding for the next phase of trials since the study was so small, the results are “exciting,” and the smaller research team allowed for cohesion of researchers all focused on finding vaccines for diseases larger companies often ignore.
“We’re a small group of dedicated people who really all have the same goal, and that’s really vaccines for for people who need the most and specifically for diseases that really no one else is paying attention to,” Diemert said.
Hookworm actively infects over 400 million people worldwide and is a leading cause of anemia — low levels of healthy red blood cells — in low-income tropical countries because it thrives in warm, moist climates, like Nigeria and Ethiopia, and disproportionately impacts children and pregnant women. The parasite enters the body through the skin, settles in the intestine and feeds on blood causing a slow, cumulative illness that is rarely fatal but can stunt cognitive development and growth over the years.
The trial — funded by the National Institute of Allergy and Infectious Diseases — enrolled 39 healthy adults in D.C. who had never been infected with hookworm and assigned 29 to receive one of three versions of the vaccine and 10 to receive a placebo before exposing them to hookworm larvae.
Parasites are harder to vaccinate against than many viruses or bacteria due to their genetic diversity and constantly changing chemical makeup throughout their life cycle, which researchers said is why it has taken so long to develop immunizations for hookworm.
“It’s been a long coming,” Maria Elena Bottazzi, a professor at Baylor College of Medicine and co-director of Texas Children’s Hospital Center for Vaccine Development said. “It’s slowly but surely every time we have an advancement through different milestones. And this one is, of course, the pinnacle.”
The researchers developed a vaccine that targets a protein called Necator americanus glutathione S-transferase-1, or Na-GST-1, which hookworms use to digest blood. The researchers recreated the protein and injected it into the human participants, enabling them to train the immune system to generate antibodies against it, teaching the body to fight the hookworm infection
The vaccine is designed to produce antibodies against GST-1, a hookworm protein that helps the parasite digest blood. When the worm feeds on vaccinated blood, those antibodies can disrupt that process and weaken the parasite, according to the study.
Four weeks after the final dose, the researchers exposed the participants — who gave consent — to 50 infectious hookworm larvae applied to the forearm on a gauze pad and found that participants given vaccine samples rather than placebos had fewer hookworm eggs in their stool samples.
Jeffrey Bethony, laboratory director for the GW Vaccine Research Unit and co-author of the study, said the next step is finding a manufacturing partner in Brazil or another country with an established vaccine production pipeline to take the vaccine into a larger phase two field trial. He said the publication of the study now gives funders and potential partners evidence they needed to move forward.
“The next step is really to find somebody who wants to produce this on a large scale,” Bethony said.
Peter Hotez, a professor of pediatric and molecular virology at Baylor College of Medicine and the dean of the National School of Tropical Medicine, said he has been working on the hookworm vaccine project since he was an MD-Ph.D. student in the 1980s. He said the project gained momentum after the Albert B. Sabin Vaccine Institute, founded in 1993 to advance vaccine research, received $18 million from the Bill and Melinda Gates Foundation in 2000, when he became chair of microbiology at GW, making the hookworm vaccine the signature project of his time there.
The team working on this vaccine overlapped with the team that developed the COVID-19 vaccination, Corbevax, which The Texas Children’s Hospital got its first approval for in 2021.
Hotez said that the hookworm vaccine is intended to follow the same path, produced by manufacturers in low- and middle-income countries for the benefit of populations that could never afford a commercially priced product and called Hookworm a disease of the world’s “poorest people.”
“This is very much a human initiative,” Hotez said.
He said the team is now approaching what he calls the “last mile,” finding partners in lower-income countries, working out a sustainable financial model and running the field studies that would bring the vaccine toward licensure.
“In some ways the biggest hurdles are not necessarily just the scientific ones,” Hotez said. “There’s all the complexity of, not many groups have developed a product for people living in extreme poverty. So there’s no obvious roadmap for this.”
Lara Hoeweler, laboratory manager and GW alum who has worked in Bethony’s lab since she was an undergraduate, tested blood samples drawn from participants at multiple timepoints to measure their antibody responses to the vaccines. She said working on the project gave her a sense of purpose that clinical processing work often lacks because of the lack of patient interaction.
“It feels good to do something,” Hoeweler said. “When you feel like you’re doing something your not just clocking in and getting a paycheck.”
