{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/11284"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/11284","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"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","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Tiner, Bethany L"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Microbiology and Immunology (Doctoral)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Chopra, Ashok"],"committee_chairs":[],"committee_members":["Motin, Vladimir","Peterson, Johnny","Cong, Yingzi","Tesh, Vernon"],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:50:48Z","subjects":["Yersinia pestis","plague","live-attenuated vaccine","Lpp","MsbB","Ail","Pla"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/11284","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Chopra, Ashok"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Motin, Vladimir","Peterson, Johnny","Cong, Yingzi","Tesh, Vernon"]},{"key":"dc:creator","label":"Author","values":["Tiner, Bethany L"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-04-21T15:55:15Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-04-21T15:55:15Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Microbiology and Immunology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Yersinia pestis","plague","live-attenuated vaccine","Lpp","MsbB","Ail","Pla"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/11284"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Induction of Long-Term Immune Responses to Protect Mice against Pneumonic Plague: Development and Testing of Novel Live-Attenuated Mutants of Yersinia pestis CO92"]}]}],"canonical_facts":{"dc:contributor.advisor":["Chopra, Ashok"],"dc:contributor.committeemember":["Motin, Vladimir","Peterson, Johnny","Cong, Yingzi","Tesh, Vernon"],"dc:creator":["Tiner, Bethany L"],"dc:date.accessioned":["2021-04-21T15:55:15Z"],"dc:date.available":["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","plague","live-attenuated vaccine","Lpp","MsbB","Ail","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"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Microbiology and Immunology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:50:48Z"}