Jessie Cheung, Staff Photographer

Researchers at the Yale School of Public Health have identified a vaccine candidate against the potentially deadly Leptospira bacteria.

Leptospira bacteria are responsible for causing both leptospirosis, a relatively mild infection, and Weil’s disease, which can be fatal. Humans contract the bacteria when they come into contact with the urine of infected rodents, dogs or farm animals. There are approximately 300 strains of disease-causing Leptospira bacteria, all of which use a protein known as FcpA for movement and host infection, according to associate research scientist in epidemiology Elsio Wunder.

Wunder and colleagues at YSPH found that live but attenuated Leptospira bacteria lacking the FcpA protein could confer long-lasting immunity when injected into mice and hamsters. The results were published in the journal eLife and indicate that this construct could serve as the first vaccine candidate of its kind against the deadly bacteria.

“[Leptospirosis] is the leading zoonotic disease in terms of morbidity and mortality worldwide as per reports,” postdoctoral associate Karukriti Kaushik Ghosh, who has been involved in follow-up research to this study at YSPH, wrote in an email to the News. “The study’s primary purpose was to identify an effective single-dose universal vaccine that could protect against most [Leptospira bacteria] … and provide a solution to the health challenges caused by leptospirosis.”

Ghosh explained that without treatment, leptospirosis can cause kidney failure, meningitis, liver failure and even death. Former postdoctoral associate at the YSPH Camila Hamond said that when humans become infected by the bacteria, they may exhibit flu-like symptoms. Research assistant at the YSPH Cate Muenker added that while these symptoms can be treated with antibiotics, if left unchecked this infection can worsen and result in more severe, potentially fatal complications from Weil’s disease.

Wunder elaborated on the importance of this research in a global context. He explained that although the burden of leptospirosis primarily falls on individuals experiencing poor sanitation conditions and a lack of potable water in countries with lower gross national incomes, there have been outbreaks in the United States in recent years.

Wunder noted that from 2017 to 2018, there were three reports of leptospirosis among residents in New York City. Additionally, a large epidemic of the disease erupted in Puerto Rico in the wake of Hurricane Maria due to the subsequent disruption to sanitation in the area. Wunder predicts that the prevalence of leptospirosis will increase in the future due to the pressures of climate change and global poverty.

“The burden of leptospirosis is likely to increase, as extreme weather events intensify in frequency with global climate change, increased social inequalities and the prediction to double the urban slum population worldwide,” Wunder wrote in an email to the News.

In the study, researchers first identified the novel FcpA protein, which enables Leptospira bacteria to infect animals and humans by prying apart and penetrating cell membranes. Then, Ghosh described, the scientists mutated the gene that codes for this motility protein so that it could no longer break into cells. When they injected this construct into mice and hamsters, the rodents’ immune systems mounted a suitable response and the attenuated virus did not result in disease.

Ghosh said that the researchers also wanted to test whether the vaccine candidate would confer protection against several species of Leptospira bacteria. They found that this vaccine candidate provided significant protection against three different species.

“For the first time, the team has shown that a universal leptospirosis vaccine candidate can prevent both death and kidney colonization in laboratory animal models,” Ghosh wrote.

Although another vaccine against Leptospira is currently available for animals and serves as the main measure to minimize transmission of Leptospira from animals to humans, Wunder explained that this existing vaccine does not prevent the bacteria from colonizing kidneys of infected hosts.

Wunder explained that in contrast, his team’s vaccine candidate prevents renal colonization and thus has the potential to block interspecies transmission by reducing bacterial levels in infected animals. Muenker added that because Leptospira attach to the kidney and are shed through urine back into soil and water reservoirs, preventing the proliferation of Leptospira bacterial cells in the kidney is crucial to prevent the spread of leptospirosis.

“This strong immune response [induced by the vaccine candidate] was … able to protect mice against renal colonization, which can prevent animals from spreading the bacteria [to] the environment,” Wunder wrote.

The study’s results also showed a robust antibody response in the rodents’ immune system after injection with the vaccine candidate, according to Ghosh. This response revealed 41 different proteins that could potentially serve as targets for future vaccines.

Ghosh is currently studying these proteins of interest in greater detail and is working to make the vaccine candidate available commercially for animal health care.

Additionally, Wunder is collaborating with a veterinary company to study the efficacy of the vaccine candidate in other animals.

The Centers for Disease Control and Prevention estimate that more than 59,000 deaths and one million cases of leptospirosis occur annually around the globe.

Sydney Gray | sydney.gray@yale.edu