Having recently discovered the toxin that causes the tropical disease leptospirosis to be so lethal, a Yale research team has developed a vaccine that prevents the disease while nearly eliminating the deadly bacteria from the body.
The team, led by Joseph Vinetz, MD, professor (infectious diseases) in the Department of Internal Medicine at Yale School of Medicine (YSM), and Reetika Chaurasia, postdoctoral associate at YSM, used the genome project to identify the Leptospira-secreted protein exotoxin as the leading candidate for how leptospirosis kills. They then showed that vaccination with the toxin eliminated the disease, and an antibody neutralized the toxins in preclinical models. They report their findings in a scientific manuscript that has been accepted for publication in Frontiers in Cellular and Infection Microbiology.
The development of a vaccine for leptospirosis would have huge implications for global public health, said Vinetz, the paper’s senior author, with the greatest impact being in developing countries where there is a higher disease burden that is completely unmet. Leptospirosis, he said, “is a neglected tropical disease that causes people to die of hemorrhagic fever despite antibiotics. This is a disease that needs a vaccine.”
The research team tested the hypothesis that immunization of mice with a family of proteins called VM proteins would protect against lethal infection and reduce bacterial load in the liver and kidneys. They found that the immunized mice were protected from lethal infection and had a reduced bacterial load in those organs.
The bacterium that causes leptospirosis permanently colonizes the renal tubules of the kidneys of animals. The vaccine protects these tiny tubes, which return filtered nutrients and fluids back to the blood with the remaining fluid and waste being expelled as urine. Humans and animals become infected with leptospirosis after being exposed to the urine of infected animals — such as rats and dogs — in mud or water, which can get into wounds, the eyes, or be swallowed.
Leptospira can cause life-threatening conditions in humans, including Weil syndrome and lung hemorrhage. It’s especially prevalent among the world’s most impoverished populations in tropical countries where there are frequent hurricanes and flooding. Uncontrolled sewage and limited animal vaccinations cause the disease to spread further. Although leptospirosis is not a public health concern in the US, the disease infects millions of people throughout the world yearly, according to estimates.
Yale has patented the intellectual property in the scientific manuscript, and Yale Ventures has agreed to terms to license the technology to LeptoX BioPharma, a startup company Vinetz co-founded, a potential conflict of interest that he notes in the manuscript. The next step is to translate the laboratory discovery into vaccines, first for animals and then for humans.
In addition to Vinetz and Chaurasia, the Yale researchers who contributed to the manuscript, “Vaccination with Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice from Severe Leptospirosis and Reduces Bacterial Load in Liver and Kidney,” are post-baccalaureate Aryeh Salovey , Xiaojia (Sasha) Guo, PhD, associate research scholar in medicine (nephrology), and Gary Désir, MD, Paul B. Beeson Professor of Medicine (nephrology) and chair of the internal medicine department at YSM.
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