Immunocontraceptive vaccines against brucellosis and population growth in feral swine

Simple item page
dc.contributor.authorSmith, Garrett Paulen
dc.contributor.committeechairSriranganathan, Nammalwaren
dc.contributor.committeememberBoyle, Stephen M.en
dc.contributor.committeememberClark-Deener, Sherrieen
dc.contributor.committeememberLarson, Timothy J.en
dc.contributor.departmentVeterinary Medical Sciencesen
dc.date.accessioned2017-06-09T18:30:41Zen
dc.date.adate2016-10-26en
dc.date.available2017-06-09T18:30:41Zen
dc.date.issued2016-10-03en
dc.date.rdate2016-10-26en
dc.date.sdate2016-10-13en
dc.description.abstractFeral swine are a nuisance species across the United States that costs around $1.5 billion each year in agricultural, environmental, and personal property damages. In the last ten years the population of feral swine is estimated to have quadrupled and novel population control methods are needed. Furthermore, feral swine are known carriers of zoonotic diseases such as brucellosis, which threatens both livestock biosecurity and public health. Recombinant multimeric gonadotropin-releasing hormone (mGnRH) has been previously used as a subunit vaccine to induce immunocontraception in feral pigs. However, potent adjuvants and large amounts of purified antigen are needed to elicit a robust anti-GnRH immune response and current delivery methods are limited. Brucella suis strain VTRS2 can be used as a novel platform to deliver mGnRH without the use of antibiotic resistant markers. Strain VTRS2 was created by deletion of the LPS biosynthesis gene wboA as well as the leuB gene required for leucine biosynthesis inside the nutrient-depleted intracellular environment occupied by Brucella. Mutations in wboA are known to attenuate Brucella strains such as the vaccine strain B. abortus RB51, however strain RB51 is rifampin resistant and has poor efficacy in swine. Strain VTRS2 confers significant protection against B. suis challenge in mice and additionally shows evidence of protection in feral swine. Furthermore, the mGnRH antigen can be delivered using the pNS4 plasmid (which expresses leuB under its native promoter) thus maintaining the plasmid in strain VTRS2 under leucine-deficient conditions while expressing recombinant antigen in the host. The murine model was used to determine the clearance kinetics of strain VTRS2-mGnRH and to measure vaccine efficacy against challenge by virulent B. suis 1330. Subsequently the effects of the VTRS2-mGnRH vaccine on fertility were assessed in breeding trials in mice. Strains VTRS2 and VTRS2-mGnRH were found to be protective against virulent Brucella suis challenge. Strain VTRS2-mGnRH elicited an anti-mGnRH antibody response in vaccinated mice, though an effect on fertility was not observed. An improved vaccine against brucellosis in swine, which also confers immunocontraception without the introduction of antibiotic resistance, could become an important tool in the management of this nuisance invasive species.en
dc.description.abstractgeneralFeral swine (<i>Sus scrofa</i>) are a major invasive species in the United States. Their population is estimated to have quadrupled in the past ten years and their geographic range has expanded to include at least 39 states. In addition to causing over $1.5 billion annually in agricultural, environmental, and property damages, feral swine also carry several diseases of public health and agricultural significance including influenza, leptospirosis, and brucellosis. Among these diseases, brucellosis, caused by the bacterial organism <i>Brucella suis</i>, is of particular concern because of its ability to cause reproductive losses in domestic swine and cattle as well as a debilitating febrile illness in humans. The disease has been eradicated from domestic livestock in the United States, and reintroduction could have severe consequences for both animal agriculture and public health. With the continued expansion of the feral swine population, the potential for spillover of disease into domestic livestock and humans increases. Additional tools are therefore needed to aid in both population and disease control. Immunocontraceptive vaccines have previously been used to reduce population growth in wildlife, and have been proposed for use in feral swine. Immunocontraceptives work by introducing an immunogenic form of a reproductive hormone which then causes an autoimmune response against the natural form of the hormone produced by the animal. This work describes the development of the <i>B. suis</i> vaccine strain VTRS2-mGnRHb, which was created from a virulent strain of <i>B. suis</i> to make an attenuated live vaccine capable of delivering the immunocontraceptive antigen mGnRH. The goals of strain VTRS2 were to act as a vaccine which protect against virulent <i>B. suis</i> challenge and which confers an infertility effect in the mouse model. An improved vaccine against brucellosis in feral swine, which also confers an infertility effect, could become an important tool in the management of this nuisance invasive species.en
dc.description.degreePh. D.en
dc.identifier.otheretd-10132016-175201en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-10132016-175201/en
dc.identifier.urihttp://hdl.handle.net/10919/77987en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectimmunocontraceptionen
dc.subjectvaccineen
dc.subjectbrucellosisen
dc.subjectBrucellaen
dc.subjectferal swineen
dc.subjectmouse modelen
dc.subjectmGnRHen
dc.subjectinfertilityen
dc.titleImmunocontraceptive vaccines against brucellosis and population growth in feral swineen
dc.typeDissertationen
dc.type.dcmitypeTexten
thesis.degree.disciplineVeterinary Medical Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
etd-10132016-175201_Smith_GP_D_2016.pdf
Size:
1.83 MB
Format:
Adobe Portable Document Format
Download

Collections

Doctoral Dissertations