Yale School of Public Health scientists have helped to design a proof-of-concept vaccine that could protect against a family of bacteria known to cause 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. Their test results were published in the journal eLife earlier this year.
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 catch 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 for a family of bacteria with around 300 different varieties, coming up with a universal vaccine has proven challenging. Researchers need to find a common feature among all the bacteria that will trigger an immune response for the cure to work. In this study, however, scientists at YSPH and at laboratories across the world have found a potential 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 first author and YSPH Associate Research Scientist Elsio Wunder Jr., Ph.D.
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.
Albert Ko
The test results are promising. After the lab-grown Leptospira was given to hamsters and mice, it spread throughout the body and trained their cells to fight back against 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.
To determine whether the vaccine candidate could protect against all types of Leptospira infection, they tested a single dose of the engineered Leptospira and compared its success against heat-killed Leptospira. Immunization with the heat-killed vaccine gave only partial protection against certain variants and failed to help in others. On the other hand, the researchers’ vaccine candidate provided cross-protection against the majority of variants that pose a threat to humans and animals.
The engineered vaccine also helped to generate antibodies that recognized a wide range of proteins across the different species of Leptospira. And after further analysis, the research team found other proteins that could also work as universal vaccines.
“In this proof-of-concept study, we have shown that a universal leptospirosis vaccine candidate can prevent both death and kidney colonization in animal models,” said YSPH Professor Albert Ko, M.D., who was senior author for the study. “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 and can be deployed as a broad solution to the human and animal health challenge caused by leptospirosis.”