Induction of Long-Term Immune Responses to Protect Mice against Pneumonic Plague: Development and Testing of Novel Live-Attenuated Mutants of Yersinia pestis CO92
| dc.contributor.advisor | Chopra, Ashok | |
| dc.contributor.committeeMember | Motin, Vladimir | |
| dc.contributor.committeeMember | Peterson, Johnny | |
| dc.contributor.committeeMember | Cong, Yingzi | |
| dc.contributor.committeeMember | Tesh, Vernon | |
| dc.creator | Tiner, Bethany L | |
| dc.creator.orcid | 0000-0002-9567-3894 | |
| dc.date.accessioned | 2021-04-21T15:55:15Z | |
| dc.date.available | 2021-04-21T15:55:15Z | |
| dc.date.created | 2016-08 | |
| dc.date.submitted | August 2016 | |
| dc.date.updated | 2021-04-21T15:55:15Z | |
| dc.description.abstract | Currently, there is no FDA-approved vaccine against the causative agent of the pneumonic plague, Yersinia pestis. Since both humoral and cell-mediated immunity are essential in providing protection against the plague, we developed three novel live-attenuated vaccine strains. These mutants were either deleted for genes encoding Braun lipoprotein (Lpp), an acetyltransferase (MsbB), the attachment invasion locus (Ail), and/or the plasminogen-activator protease (Pla) creating the Δlpp ΔmsbB Δail and Δlpp ΔmsbB Δpla triple mutants of Y. pestis CO92. Another stain containing a modified version of the ail gene with diminished virulence (Δlpp ΔmsbB::ailL2) was also developed. All three live-attenuated mutants were highly attenuated (100% survival) in mice after intranasal, intramuscular, and/or subcutaneous administration suggesting these vaccine candidates are safe with no untoward clinical symptoms or histopathological lesions in various organs. These live-attenuated mutants were able to stimulate both long-term humoral- and cell-mediated immune responses, which protected mice against exposure to highly lethal pneumonic challenge with wild-type Y. pestis CO92 strain. In summary, the ∆lpp ∆msbB ∆ail, ∆lpp ∆msbB::ailL2, and ∆lpp ∆msbB ∆pla live-attenuated mutants are viable vaccine candidates; however, future studies involving immunocompromised mice as well as evolutionary higher animal models of pneumonic plague are needed to further determine the efficacy and safety of these potential live-attenuated plague vaccines. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/2152.3/11284 | |
| dc.subject | Yersinia pestis | |
| dc.subject | plague | |
| dc.subject | live-attenuated vaccine | |
| dc.subject | Lpp | |
| dc.subject | MsbB | |
| dc.subject | Ail | |
| dc.subject | Pla | |
| dc.title | Induction of Long-Term Immune Responses to Protect Mice against Pneumonic Plague: Development and Testing of Novel Live-Attenuated Mutants of Yersinia pestis CO92 | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Microbiology and Immunology | |
| thesis.degree.grantor | The University of Texas Medical Branch at Galveston | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Microbiology and Immunology (Doctoral) |