Oregon FNAWS
Sheep - Sheep Research
On-going Research with the funds from OR-FNAWS and other Chapters
  1. Prevention of transmission of pneumonia-causing bacteria from domestic sheep to bighorn sheep.
    Most of the domestic sheep carry pneumonia-causing organisms (harmful organisms) in their tonsils. Domestic sheep are resistant to these harmful organisms, but the bighorn sheep are not. Therefore, when these harmful organisms (leukotoxin-producing Mannheimia haemolytica) are transmitted to bighorn sheep when the two species commingle, bighorn sheep develop pneumonia and die. Studies in my laboratory have shown that the growth of the harmful organisms can be inhibited by another harmless organism (leukotoxin-negative Bibersteinia trehalosi) that does not cause pneumonia. If we can eliminate or reduce the harmful organisms in the tonsils of domestic sheep, we could potentially eliminate or reduce the shedding of the harmful organisms by the domestic sheep and hence eliminate or reduce the risk of domestic sheep causing pneumonia in bighorn sheep.
    Sheep Research 1
    Progress: In previous studies, inoculation of the harmless organism into the throats of domestic sheep reduced the number of harmful organisms in the tonsils of domestic sheep, but the reduction was not adequate. Therefore, we first inoculated the domestic sheep with an antibiotic to eliminate the harmful organisms. This resulted in much greater reduction in the number of the harmful organisms. We then inoculated the domestic sheep with the harmless organism. We then commingled the harmless organism-inoculated domestic sheep with bighorn sheep to determine whether the treatment of the domestic sheep with the antibiotic and the harmless organism will prevent/reduce the transmission of the harmful organisms to bighorn sheep.
    In another facet of this project, we are working on identifying the substance produced by the harmless organism that inhibits the growth of the harmful organism. Why? If we identify that particular substance, we can induce the harmless organism to produce more of that substance which should result in more effective inhibition of the growth of the harmful organism.
  2. Understanding the reasons for poor lamb recruitment in the herds that suffered pneumonia die-off.
    When a pneumonia die-off occurs, bighorn sheep of all ages die. In subsequent years, the adult bighorn sheep rarely die, but the lambs continue to die year after year, and hence the herds do not grow in numbers. We are working on understanding the reasons underlying this phenomenon.
    Progress: Our previous research with the Nevada bighorn sheep that survived a pneumonia outbreak has revealed that these animals remained as carriers, which means that they carry the disease-causing organisms (mainly, Mannheimia haemolytica and Mycoplasma ovipneumoniae) but do not develop the disease. When commingled with naïve (uninfected) bighorn ewes from our captive herd, they became infected with the disease-causing organisms, but did not die (except for one ewe). All the lambs born to the infected ewes got infected, developed pneumonia, and died. The survivor ewes may have immunity to the harmful organisms, but it may not be adequate to pass on to their lambs.
    For the information to be meaningful, we should study survivor ewes from different geographical locations. Therefore, last year we repeated the study with another group of survivor ewes from Colorado, housed in Sybille, WY. The results of this study were similar to that we obtained with the Nevada animals. In this study, we attempted to eliminate the "carrier status" of the ewes by antibiotic treatment. However the antibiotic treatment was not effective because of the delay in the injection of antibiotic due to unavoidable reasons. This year we will determine the efficacy of the use antibiotics and/or vaccination in the elimination of the carrier status. For this study, we have received six bighorn ewes from a herd that suffered pneumonia-related die-off in Montana. This study should provide information useful in designing management strategies.
  3. Development of a vaccine to protect bighorn sheep against the harmful organisms that cause pneumonia.
    The main weapon used by one of the harmful organisms that cause pneumonia is a toxic substance (leukotoxin) produced by this organism. We are working on developing a vaccine that will consist of a harmless virus that carries a portion of this toxin. When this virus infects an animal, it will continue to remain inside the animal in an inactive form (latency), but will become the active form (reactivation) once in a while. When it becomes the active form, it replicates. When it replicates, the portion of the toxin that it carries will also be produced. This is equivalent to giving a booster injection of the vaccine. Thus the animals need not be given repeated injections. Another advantage of this 'virus-vectored' vaccine is that it will be shed and hence transmitted from the vaccinated bighorn sheep to un-vaccinated bighorn sheep in the wild. Since this virus is modified and weakened, it is harmless to the animals, but the toxin portion that it carries will induce protection against the organism that produces the toxin and causes pneumonia. This vaccine should be useful to immunize bighorn sheep at the time of translocation to re-populate a region. Vaccinated and protected bighorn sheep are more likely to survive and grow in numbers, than unprotected bighorn sheep. If successful, an oral/nasal version of the vaccine could be developed which will eliminate the need for needle immunization which obviously is not practical in wildlife.
    We selected bovine herpesvirus 1 to develop this vaccine. Herpesviruses have large genomes which are amenable to insertion of foreign genes. Another advantage of bovine herpes virus 1 is that it undergoes latency and subsequent reactivation, which means that the vaccine virus will remain latent in the body with subsequent reactivation. During reactivation, along with the viral proteins, the Mannheimia haemolytica antigens will also be produced, which is equivalent to giving a booster dose of the vaccine. Another advantage is that the virus is shed by the immunized animals during reactivation. It is likely that the shed virus will immunize the unimmunized animals in the vicinity.
    Although bovine herpesvirus1does not cause disease in bighorn sheep, we are using an attenuated mutant bovine herpesvirus 1 developed in our laboratory. In a pilot study, one bighorn sheep was inoculated with the mutant virus. The mutant did not cause any clinical signs of disease except elevated rectal temperature for one day, indicating the safety of this virus as a vaccine virus. The mutant virus-inoculated bighorn sheep shed the virus. It also underwent latency in the inoculated bighorn sheep.
    We have identified the immunogenic domain (the domain that will induce an immune response) of the leukotoxin and an outer membrane protein of Mannheimia haemolytica. In the coming months, we will insert the immunogenic domain of the leukotoxin and an outer membrane protein of Mannheimia haemolytica into the virus vector to construct the vaccine virus that will deliver the immunogenic domain of the leukotoxin and outer membrane protein to the animals that vaccine virus.
Srikumaran's research team consists of three PhD graduate students and one research assistant professor. All three PhD students now have graduate fellowships from Morris Animal Foundation. Seventy five percent of the salary of the research assistant professor is provided by the department (Veterinary Microbiology and Pathology). I am very grateful for the funding from the Wild Sheep Foundation, OR-FNAWS, and other chapters, and US Forest Service.
Sri Srikumaran, BVSc, MS, PhD
Professor, and Rocky Crate-FNAWS Endowed Chair
Department of Veterinary Microbiology and Pathology
College of Veterinary Medicine
Washington State University
Pullman, WA 99164-7040
Sheep Research 2
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