Seeking the "Holy Grail"

Scientists at the Yale School of Public Health are helping design a proof-of-concept vaccine that could protect against a family of bacteria responsible for deadly blood infections in humans and animals.

If successful in future trials, the vaccine candidate would be considered a “holy grail” public health intervention and could prevent thousands of deaths each year from the bacteria, known as Leptospira. The test results were published in the journal eLife.

A broad range of mammals, including rats, harbor Leptospira in their kidneys and release it into the environment through their urine. Humans and animals can get the bacteria after coming into contact with the contaminated water or soil. Once it gets in the body, Leptospira can cause life-threatening conditions, including Weil’s disease and lung hemorrhage. It’s an especially worrisome disease in the world’s most impoverished populations, infecting millions yearly according to some estimates.

But coming up with a universal vaccine for a family of bacteria with around 300 varieties has proven challenging. For the cure to work, researchers typically need to find a common feature among all the bacteria that will trigger an immune response. In this study, however, scientists at YSPH and at laboratories across the world have found a potential different solution: disabling a protein in the bacteria’s tail known as FcpA.

“With this study, we wanted to see whether using engineered Leptospira that lacks a functional FcpA molecule has the potential for a vaccine that could provide major public health benefit,” said YSPH Research Scientist Elsio Wunder Jr., Ph.D., the study’s lead author.

The results were promising. After the lab-grown Leptospira was given to hamsters and mice, it spread throughout the body and trained their cells to fight the bacteria by developing antibodies. No traces of the bacteria could be detected in the animals’ kidney tissue or blood several days later. This shows that the vaccine worked: Leptospira was killed before it could cause disease—leptospirosis–or death.

“These findings take us one step closer to achieving the holy grail for the field, which is an effective vaccine that protects against the many Leptospira species,” said YSPH Professor Albert Ko, M.D., the Raj and Indra Nooyi Professor of Public Health and the study’s senior author.