Dr. Yung-Fu Chang
Leptospirosis is caused by a group of highly invasive spiral bacteria (spirochetes) that are capable of infecting people and animals, including horses. Transmission occurs either through direct contact with an infected animal or through indirect contact with soil or water contaminated with urine from infected animals. Infection of horses with this bacterium causes uveitis (periodic ophthalmia), chronic and severe ocular pain leading to blindness, abortion, fever and icterus (jaundice). Leptospira induced uveitis is the most significant ocular disease of horses.
Currently, there is no vaccine against equine leptospirosis. Most veterinarians use commercially available vaccines for cattle. These vaccines contain heat- or formalin-killed leptospires and produce only incomplete, short-term immunity. Further, the need for an equine vaccine against leptospirosis is exemplified by recent outbreaks of the disease in New York and other States (Pennsylvania, Kentucky, and Tennessee) and the nearly world-wide incidence of Leptospira induced recurrent uveitis.
Lipoproteins have been identified in many spirochetes including Treponema pallidum, Treponema denticola, Treponema phagedenis, Serpulina hyodysenteriae, Borrelia burgdorferi, and the relapsing fever borreliae. Several surface-exposed lipoproteins from spirochetes are known to be protective immunogens. We have shown that outer surface protein A (OspA), a lipoprotein from another spirochete (Borrelia burgdorferi), can protect dogs and horses against Lyme infection and disease. Thus, it is logical that the vivo expression of surface-exposed lipoproteins of Leptospira spp. would also be immunogenic and therefore, potential candidates for vaccine development.
The construction of a recombinant vaccine against leptospirosis is hindered by the increasing number of pathogenic serovars of Leptospira. It appears that some serovars of Leptospira associated with disease outbreaks are host specific. In addition, it is very difficult to develop a safe vaccine against an infection that can induce immune-mediated disease (auto-immune disease). To develop a recombinant vaccine against leptospiral infection, it is necessary to demonstrate that immune responses directed against the vaccine candidate (recombinant antigen) will not cross-react with host tissues.
Our long-term goals are to better understand the pathogenesis of leptospirosis in horses and to develop a safe and effective recombinant vaccine against equine leptospirosis. We propose to identify the genes that are only expressed after infection. These gene products have the potential for use in novel vaccines. Also, they could be used to develop diagnostic tests that could differentiate between vaccinated animals and natural infection. As a first step toward this goal, we propose to use a novel technique (IVIAT) to identify a subset of genes expressed only during infection.