First Leishmaniasis Vaccine Using CRISPR Gene-Editing Clears FDA Hurdle, Phase 1 Trial Set to Begin
核心洞察
A Phase 1 clinical trial for the first-ever leishmaniasis (搜索) vaccine is set to begin in the coming months, testing safety in healthy volunteers across Kenya, Brazil, and potentially the United States.
The live attenuated vaccine, developed at Ohio State University using CRISPR gene-editing to delete the centrin (搜索) gene from Leishmania major (搜索), was 100% effective in animal studies.
Up to 1 million new cases of cutaneous leishmaniasis (搜索) are diagnosed annually worldwide, with approximately 1 billion people at risk across 99 endemic territories and countries, now including the U.S.
A Phase 1 clinical trial testing the safety of the world's first leishmaniasis (搜索) vaccine is set to begin in the coming months, marking a pivotal milestone in the fight against a neglected tropical disease that threatens up to 1 billion people globally. The vaccine, developed by researchers at The Ohio State University College of Medicine using CRISPR gene-editing technology, recently cleared a key regulatory hurdle with U.S. Food and Drug Administration approval as an investigational new drug (IND).
"This means the FDA has seen the product and our preclinical data and has deemed that this product can be tested in people now," said lead researcher Abhay Satoskar, professor of pathology at Ohio State. "It's a big milestone in terms of product development, especially when the product was conceived in academia."
The IND approval carries global significance. "This helps everywhere in the world because once the U.S. FDA gives its approval, it means other regulators know that it has gone through a very thorough review," Satoskar added.
CRISPR-Enabled Vaccine Design
The vaccine represents a modern refinement of leishmanization, a century-old Middle Eastern practice of deliberately introducing live Leishmania parasites to the skin to create a small, self-healing infection that confers lifelong immunity. Using CRISPR, the research team edited the genome of Leishmania major (搜索) by deleting centrin (搜索), the gene encoding a protein essential for the parasite's structural integrity.
In animal studies, the mutant parasite lacking centrin (搜索) could still enter host immune cells and replicate, but only for a limited duration and not at a pace that leads to clinical disease. Immunization with the genetically modified parasites induced robust immunity against vector-transmitted infections.
"Live vaccines like that are the best vaccines, but there's a potential risk of causing serious disease in some people," Satoskar explained. "We refined the concept using modern technology, making a parasite that does not cause clinical disease but allows for induction of immunity."
In animal studies, the vaccine was 100% effective. "It worked beautifully. It worked beyond my imagination to be honest," Satoskar said.
Disease Burden and Growing U.S. Presence
Leishmaniasis (搜索) is caused by parasites of the Leishmania genus, transmitted through the bite of infected female sand flies. The World Health Organization lists it among the top neglected tropical diseases worldwide. According to a review article published in the New England Journal of Medicine — co-authored by Satoskar alongside Naomi Aronson of the Uniformed Services University of the Health Sciences and Ahmed Musa of the University of Khartoum — up to 1 million new cases of cutaneous leishmaniasis are diagnosed annually. At any given time, approximately 6 million people are infected, and up to 1 billion people across 99 territories and countries where the disease is endemic are at risk.
The disease is now gaining ground in the United States. "Sand flies don't know borders, and more and more infected sand flies are being found in U.S. states that border Mexico," said Bradford McGwire, an infectious diseases physician and professor at Ohio State Wexner Medical Center. "In the last two years, we've seen on average two to four cases per year at Ohio State. In the past we used to see maybe one case per year. It's definitely been ticking up over time in the U.S."
The three main clinical forms include cutaneous leishmaniasis (搜索) — the most common, causing skin sores and ulcers that may take months to heal — mucosal leishmaniasis, which causes disfiguring lesions of the mouth, nose, and vocal cords, and visceral leishmaniasis, the most serious form affecting internal organs including the spleen, liver, and bone marrow, which is fatal if left untreated.
Trial Design and Global Reach
The Phase 1 trial will be conducted in Kenya and Brazil, two endemic countries targeted for eventual vaccine deployment, with a potential additional site in Cincinnati, Ohio. Between approximately 75 and 100 healthy volunteers will participate. The initial trial focuses on safety, though blood samples will be collected to assess whether the vaccine provokes an immune response. Testing in endemic regions is critical to evaluate whether individuals with prior parasite exposure — and therefore pre-existing antibodies — experience allergic reactions or other adverse effects.
Following interim analysis of Phase 1 results, the team aims to conduct a Phase 2 trial in at least 3,000 people to evaluate vaccine effectiveness and side effects.
A Parallel Diagnostic Tool
In tandem with the vaccine, Satoskar's team is developing a leishmaniasis (搜索) skin test analogous to the tuberculosis skin test. "Testing positive with the skin test means that a person has been exposed to the disease and is now immune to the disease," Satoskar said. "It is a test for immunosurveillance but also for immunogenicity of our vaccine. Without this kind of test, you cannot do surveillance. You cannot know the level of immunity in the community."
Economic and Public Health Implications
Researchers estimate the vaccine would cost less than $5 per dose, a stark contrast to the $100 to $200 cost of current treatments in the hardest-hit countries. Existing therapies require weeks of daily drug injections with unpleasant side effects, leading to poor patient compliance and the emergence of drug-resistant parasites. "An effective prophylactic vaccine is indispensable for elimination or eradication of leishmaniasis (搜索)," Satoskar said. "This is true for almost all infectious diseases."
The Phase 1 trial and skin test production are supported by $10 million in grants from the Japan-based Global Health Innovative Technology Fund (搜索), which also backed vaccine development alongside the Wellcome Trust UK (搜索). Additional partners include Nagasaki University, Gennova Biopharmaceuticals Ltd. (the vaccine manufacturer), Universidade Federal de Minas Gerais in Brazil, HJF Medical Research International in Kenya, the FDA, the National Institute of Allergy and Infectious Diseases, and Johns Hopkins University.
Satoskar and colleagues have also applied the CRISPR technique to develop a vaccine using the Leishmania donovani parasite, which causes visceral leishmaniasis (搜索), potentially extending protection against the most lethal form of the disease.