Photo: Yung-Fu Chang examines a screening of a leptospira genomic library. The dark spots on the plates are positive clones he has made of leptospiria genes.
First Steps Toward a Vaccine Against Leptospirosis
Photo: Yung-Fu Chang examines a screening of a leptospira genomic library. The dark spots on the plates are positive clones he has made of leptospiria genes.
Leptospirosis, a disease that infects humans and animals, including horses, is caused by a highly invasive spiral bacteria. In horses, leptospirosis can cause partial or total blindness, abortion, fever, and icterus (jaundice). Although there are vaccines to protect cattle, swine, and dogs that live in infected areas, there are no available vaccines approved specifically for the horse.
To lay the groundwork for a vaccine against equine leptospirosis, Yung-Fu Chang DVM,MS, PhD, Dipl ACVM, a professor of population medicine and diagnostic sciences, has received a Zweig grant to clone and characterize the genes that encode the candidate vaccine antigens.
"Most veterinarians currently use commercially available vaccines approved for cattle in horses, but these vaccines produce only incomplete, short-term immunity," says Chang. "Our long-term goal is to develop a genetic(DNA) vaccine or a recombinant vaccine against equine leptospirosis which we believe has the potential to protect against the disease without many of the disadvantages associated with vaccines presently used. Such a vaccine would involve inoculation with plasmid DNA vectors that encode immunogenetic proteins; these proteins induce both antibody and cell-mediated immune responses that provide protective immunity."
Specifically, Chang will clone and characterize the outer surface proteins (lipoproteins) of Leptospira interrogans serovar pomona type Kennewicki, which are protective immunogens and could be used to develop a leptospiral vaccine.
Although little is currently known about the surface proteins of the pathogenic bacterium associated with leptospirosis in horses, Chang says that researchers know that outer surface proteins that interact with hosts are of interest as vaccine candidates because they've been shown to be protective immunogens of bacterial diseases. In previous work, Chang has examined the outer surface protein A (OspA), a lipoprotein from another spirochete, as a DNA vaccine in mice and dogs and has studied a recombinant OspA vaccine in dogs and horses.
"We have shown that OspA can protect dogs and horses against Lyme disease and L.interrogans serovar pomona, a spirochete that expresses lipoproteins," Chang explains. "In fact, the OspA protective antigen is itself a lipoprotein. Thus, it is reasonable to speculate that one or several of the outer surface proteins of Leptospira would also be immunogenic and, therefore, be potential candidates for vaccine development."
Researchers have identified a specific protein that is an immunogenic antigen in animals experimentally infected with L.interrogans serovar pomona, which is why Chang has chosen to focus on the cloning and characterization of its lipoprotein gene as the first step in the development of a DNA and/or recombinant vaccine. Since he knows that certain antibodies generated from infection in L.interrogans serovar pomona in horses cross react with the eye, he must keep in mind that any effective genetic vaccine must be derived from antigens that are not cross-reactive with the eye.
"We plan to identify these antigens by molecular genetic techniques," he says.
Developing an equine vaccine against leptospirosis is critical because the disease has such wide-ranging effects.
The pathogen is known to cause uveitis (a potentially devastating inflammation of the internal structures of the eye, also known as periodic opthalmia or moon blindness), corneal opacity, abortion, fever, and jaundice both in experimentally infected and naturally infected horses. It is also believed to be the cause of some cases of still births, decreased milk production, kidney failure, and even death in horses.
In addition to recent outbreaks of the disease among horses in New York, Pennsylvania, and Kentucky, researchers have recently identified an increase in confirmed leptospiral abortion cases among horses, and one researcher has even shown that leptospiral placentitis is one of the most important emerging causes of equine abortion.
"It is clear that equine leptospirosis is becoming more and more of a problem because vaccination with the leptospiral vaccine for cattle has generally been ineffective," Chang points out.
Horses can contract leptospirosis by drinking water that has been infected or eating hay or grain that has been contaminated by the urine of infected horses, cattle, swine, or wildlife including skunks, rats, raccoons, foxes, opossums, and deer. The organism enters either through direct contact with blood, urine, or tissues from infected animals or through the mucous membranes of the eyes, nose, and mouth or a cut in the skin.
Until a vaccine is available, horse owners can protect their animals by preventing them from drinking stagnant water and by practicing good management of manure. Both water and manure can harbor the spirochete. Other precautions include fencing in water sources to keep wildlife out, draining wet muddy areas where horses are pastured, and disinfecting any areas where infected animals may have been.
