Brucellosis, caused by Gram-negative bacteria of the genus <i>Brucella</i>, is a zoonotic disease with global impacts on human, livestock, and wildlife health. Around 500,000 cases of human brucellosis are reported by the World Health Organization annually. Even though brucellosis has been eradicated from domestic livestock in the United States of America, the causative bacterial pathogen is still present in elk, bison, and feral swine. With the growth of free-range farming, domestic livestock and wildlife populations come into close contact, spreading the disease. Feral swine interactions are of particular concern. They carry a number of zoonotic diseases including brucellosis. As there is no commercial vaccination protocol to prevent brucellosis in wildlife and swine, interactions with these populations are especially dangerous for public health. Feral swine population is increasing nationwide even with the current population control practices. There is an urgent need for efficient control of feral swine and preventing the spread of brucellosis. To aid in the prevention of the spread of feral swine across the USA, immunocontraceptives have been employed. Over the years several candidates have been tested, but the search for the perfect vaccine is still ongoing. The monumental task includes reversibly preventing one of life’s most basic necessities, reproduction, through an oral route with no effect on non-target species.
One way that science is tackling both of these threats at once is through dual-purpose vaccines. Dual-purpose vaccines produce an immune response that targets two different pathogens, or in this case a pathogen and reproductive hormones. In the effort to produce this vaccine, more knowledge was needed in regards to <i>B. neotomae</i>. This dissertation showed that it has the ability to survive in a variety of cells from different species, in a similar manner to known virulent <i>Brucella</i> species. This is of concern when using <i>B. neotomae</i> as a vaccine, but it has also been shown that attenuated <i>B. neotomae</i> can provide protection against virulent <i>B. suis, B. abortus</i>, and <i>B. melitensis</i> challenge. This is a major finding in the effort towards a universal brucellosis vaccine. After genetic manipulation, cell culture assays, and mouse trials, several leucine auxotrophic <i>B. neotomae</i> and <i>B. abortus</i> strains show promise in the effort towards a dual-purpose vaccine. Strains of <i>B. neotomae</i> <i>ΔwboA ΔleuB</i> pNS4-trcD-fliC-Gonadotropins were discontinued in this effort towards a brucellosis immunocontraceptive dual-purpose vaccine due to lethality issues in mice. These stability and lethality issues are still under investigation. Instead, a proven stable strain of <i>B. abortus</i> RB51 (a USDA approved cattle vaccine) was used to investigate its effects on fertility in mice when expressing fliC-Gonadotropins. Strains <i>B. abortus</i> RB51 ΔleuB pNS4-trcD-fliC-porcineFSHβ (RB51LFSHβ) and <i>B. abortus</i> RB51 ΔleuB pNS4-trcD-fliC-GnRH (RB51LGnRH) confer reduced fertility characteristics in both male and female purpose bred mice. Strain RB51 ΔleuB has also been shown to protect against virulent <i>B. abortus</i> challenge in the literature. These findings warrant further investigation to determine the efficacy of these vaccine strains in swine as an oral vaccine. Ultimately, their ability to prevent brucellosis, while causing immunocontraception needs to be determined in feral swine. / Ph.D. / While brucellosis has been eradicated from domestic livestock in the United States, the causative agent is still present in wildlife like elk, bison, and feral swine. The interactions between these infected wildlife populations with domestic livestock and human populations pose a great health risk. Many tools are employed to mitigate these interactions including vaccination programs and population management. In particular, the feral swine population has proven difficult to control. It has quadrupled in the past ten years and continues to expand nationwide, making their population control an important national objective. Furthermore, feral swine are known carriers of zoonotic diseases, including hemorraghic colitis, leptospirosis, trichinosis, swine influenza, and brucellosis. Many cases of these diseases in humans have been traced back to interactions with feral swine. The current population control practices have failed to minimize the $1.5 billion of damage they cause to the agricultural industry per year. Thus, there is a need to effectively control the feral swine population and prevent the spread of zoonotic diseases like brucellosis. Rough leucine auxotrophic strains of <i>Brucella</i> expressing gonadotropin releasing hormone (GnRH) or porcine follicle stimulating hormone beta subunit (FSH) conjugated to <i>Salmonella</i> fliC show promise. They have been shown to provide protection from virulent Brucella strain challenge and reduce fertility characteristics in mice. Their effectiveness as an immunocontraceptive for feral swine management, while reducing the spread of brucellosis needs to be tested in swine. These vaccine strains [<i>B. abortus</i> RB51 ΔleuB pNS4-trcD-fliC-porcineFSHβ (RB51LFSHβ), <i>B. abortus</i> RB51 ΔleuB pNS4-trcD-fliC-GnRH (RB51LGnRH) and <i>B. neotomae ΔwboA ΔleuB</i> pNS4-trcD-fliC-GnRH (BNWLGnRH)] could pave the way for effective novel immunocontraceptive tools to be used in wildlife management.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/99986 |
| Date | January 2020 |
| Creators | Waldrop, S. Grant |
| Contributors | Biomedical and Veterinary Sciences, Sriranganathan, Nammalwar, Boyle, Stephen M., Burgess, Brandy A., Caswell, Clayton C., Prater, M. Renee |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International, http://creativecommons.org/licenses/by-nc-sa/4.0/ |
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