It has been decades since the last case of hookworm was reported in the United States, but the intestinal parasite still infects more than 500 million people throughout the developing world.
On the surface, the groundbreaking research being performed by Jeff Bethony, Ph.D., and David Diemert, M.D., which involves bringing hookworm back to the United States, may seem counterproductive. But they’re well on their way to developing a vaccine that could eradicate this persistent tropical disease worldwide.
After more than 15 years of research, Bethony and Diemert, both associate professors of microbiology, immunology, and tropical medicine at GW’s School of Medicine and Health Sciences (SMHS), are currently conducting first-in-human studies of two hookworm vaccine candidates, Na-GST-1 and Na-APR-1. A vaccine for hookworm — a disease that causes anemia and can lead to problems with physical and cognitive development in children — could revolutionize the way it is controlled.
The current strategy is based on mass drug administration, an approach in which anti-worm drugs are given to all children in endemic areas once a year. Diemert says that in addition to being logistically challenging, the strategy is ineffective. “Kids get re-infected after they are treated,” he says. “And there is evidence that the drugs become less effective over time.”
For these reasons, Bethony and Diemert are focused on developing a vaccine that would prevent serious hookworm infections from occurring in the first place. Their unique approach is to attenuate the nutritional process of the hookworm — effectively starving it out. “It’s a very new, novel way of creating an anti-parasite vaccine,” Bethony says. With support from the Sabin Vaccine Institute Product Development Partnership (formerly known as the Human Hookworm Vaccine Initiative), Bethony and Diemert are developing the first challenge model that has ever been done for hookworm. “This will allow for early assessment of proof of concept,” Diemert says of the Phase 1 clinical trial, which is proposed to take place at the GW Medical Faculty Associates.
After undertaking a safety feasibility study with oversight from the U.S. Food and Drug Administration and GW’s Institutional Review Board, the researchers will inoculate healthy volunteers with their candidate vaccine. They will then give the volunteers an effective dose of hookworm larvae, which is transmitted through skin penetration, to test for the protective effect of the vaccine.
“This will help us enormously as far as speeding up the timelines for allowing decisions to be made as to which vaccine candidates are the most promising,” Diemert says. There are currently two vaccines in consideration, which they plan to combine into a single product. Bethony adds that once this model is established, “if any other hookworm vaccines come along, this will be the basis on which they’ll test it.”
Although the U.S. “challenge” study is still more than a year off, Bethony and Diemert have already begun a Phase 1 clinical trial of Na-GST-1 in the state of Minas Gerais in southeastern Brazil, where they’ve been working in conjunction with the Ministry of Health since 2003.
There, they’ve built a lab and a clinic in partnership with the Oswaldo Cruz Foundation (FIOCRUZ), which houses a staff of more than 30 people, including clinicians, nurses, regulatory affairs specialists, lab technicians, and researchers. The Brazilian government, very supportive of the initiative, recently gave FIOCRUZ a $1 million grant to conduct additional clinical trials of the hookworm vaccine.
Back in the United States, Bethony and Diemert are excited to be making plans for the clinical trials to begin at GW. “It’s a big step for us to do vaccine studies here,” Bethony says. “It really integrates us. We use the whole GW infrastructure and get to involve more faculty.” John Hawdon, Ph.D., associate professor of microbiology, immunology, and tropical medicine at SMHS, will be managing the sampling of the pathogen when it arrives here in Washington, D.C.
Bethony and Diemert are especially grateful for the funding they’ve received for another Phase 1 trial of Na-GST-1 from GW, through the Clinical and Translational Science Award (CTSA) program. This study is currently underway at Children’s National Medical Center and has enrolled more than 20 healthy adult volunteers. “The pilot funding from the CTSA has been critical,” Bethony says. “It allowed us to establish a clinical structure, learn how to recruit in D.C., and train our lab in how to receive samples and work on human biomaterial.”
“It’s important in terms of vaccine development, too,” Diemert adds. “We’re testing different formulations and different ingredients to see if we can fine-tune immune response. It’s contributing to us being able to make a better vaccine.”