Immunocontraceptive vaccines against brucellosis and population growth in feral swine
Smith, Garrett Paul
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Feral 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.
- Doctoral Dissertations