As little as four years ago leptospirosis didn't seem to be a particularly importantdisease in horses.

 “It was considered only one of many possible causes of uveitis, a painful and debilitating eye disease and as a rare cause of abortion in mares,” says equine clinician Thomas Divers, DVM, Dipl ACVIM, ACVECC. 

But new diagnostic techniques have changed all that in showing that nearly all cases of equine recurrent uveitis (ERU) is caused by this infection.  

“ERU, which is also known as moon blindness, is an extremely painful, very devastating, recurring, and progressive eye disease that can rarely be cured and leads to partial or complete blindness,” Divers says.   “Infection with Leptospira also can lead to fever, jaundice (icterus), abortions, and even death.”

Now Leptospira-induced uveitis is considered the most important eye disease in horses. Although there is a vaccine for leptospirosis for dogs, swine, and cattle, this spiral-shaped bacterium is a growing problem for horse owners because there's no vaccine available specifically for horses.

“The need for an equine vaccine against leptospirosis is exemplified by recent outbreaks of abortions in New York, Pennsylvania, and Kentucky, and the nearly worldwide incidence of Leptospira-induced recurrent uveitis,” says principal investigator Yung-Fu Chang, DVM, PhD, Dipl ACVM, a molecular microbiologist and professor of population medicine and diagnostic sciences.  In addition to Divers, Chang's collaborators in vaccine development studies include pathologist Sean McDonough, DVM, PhD, epidemiologist, Hussni Mohammed, DVM, PhD, and research associate Raghavan Palaniappan, PhD.

To trigger immune response in the host, many vaccines use the entire cell (bacteria) or viral particles of the invading bacteria or virus.  However, in the case of leptospirosis, horses produce some antibodies against the whole cell that actually react against healthy eye tissues, an example of an autoimmune reaction. Thus, adverse effects could occur using a vaccine with the whole-cell bacterium.

To develop an effective and safe vaccine against equine leptospirosis, Chang had been trying to identify the bacterial surface proteins that don't express in laboratory culture, but do express when the bacteria infect animals. Recently, he made a major breakthrough by successfully pinpointing and isolating critical surface proteins (LigA, LigB, and LigC) from a virulent strain of Leptospira interrogans that was critical for infection and immunity but does not cross-react with the eye.

"The need for an equine vaccine against leptospirosis is exemplified by recent outbreaks of abortions in New York, Pennsylvania, and Kentucky, and the nearly worldwide incidence of Leptospira-induced recurrent uveitis.”

-Yung-Fu Chang

Using molecular genetic techniques, Chang successfully cloned and characterized the gene that expresses LigA and LigB, which is a critical step toward developing a DNA and/or recombinant vaccine.

“LigA and LigB proteins could be important virulence factors of this organism that is related to disease,” Chang says. His laboratory has been able to produce the protein and use it as a recombinant vaccine, which they have tested in hamsters and have found to be protective against infection and disease.

In the next phase, they will first continue to test the vaccine in hamsters to determine optimal doses and a vaccine protocol.  Then, they will develop a natural infection model, which will require infecting the eyes of horses directly, monitoring the subsequent antibody production, and assessing pathology.  After that, they will be ready to test the vaccine in horses.

“At this point, clinicians can't tell with a blood test whether a horse has been exposed to a pathogenic strain of Leptospira or has antibodies from a vaccination,” Chang explains. “Hopefully, work with this protein will prove useful not only for a vaccine but also for such diagnostic purposes.”