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Novel strategies to control transmission of\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      to humans via ticks are critical for the prevention of LD. One such strategy is to leverage non-infectious mutant strains of\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      for pathogen-derived biologics to block\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      transmission during the natural infectious cycle. Deletion of\n                      <jats:underline>B<\/jats:underline>\n                      orrelia host-\n                      <jats:underline>ad<\/jats:underline>\n                      aptation\n                      <jats:underline>R<\/jats:underline>\n                      egulator (\n                      <jats:italic toggle=\"yes\">\u0394badR<\/jats:italic>\n                      ) and replacement of eight conserved residues with alanines in Carbon Storage Regulator A of\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      (8S) resulted in mutants with upregulation of RpoS and several immunogenic lipoproteins, that were incapable of colonization in C3H\/HeN mice. Intradermal vaccination of mice with the live mutant strains resulted in significant anti-borrelial antibody responses and a reduction in\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      acquisition by na\u00efve\n                      <jats:italic toggle=\"yes\">Ixodes scapularis<\/jats:italic>\n                      larvae following needle challenge with\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      B31-A3. While vaccination with the\n                      <jats:italic toggle=\"yes\">\u0394badR<\/jats:italic>\n                      mutant conferred a significant reduction in the percentage of infected mice, ML23 and 8S mutants conferred variable levels of protection. Comparative proteomic analysis of purified borrelial lipoproteins (PBLs) from parental and mutant strains revealed similar and unique antigenic components. Infection-derived mouse serum and serum from Lyme disease patients exhibited reactivity to lysates and PBLs from these mutants. Immunization with PBLs from B31-A3 and 8S strains conferred significant protection against challenge with\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      -infected nymphs, underscoring the utility of PBLs as protective formulations. Overall, non-infectious mutant strains, or their lipoproteins, can be exploited as biologics to block the acquisition of\n                      <jats:italic toggle=\"yes\">Bb<\/jats:italic>\n                      by na\u00efve larvae from reservoir hosts, thereby disrupting the enzootic transmission cycle of the agent of Lyme disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00210-26","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:10:38Z","timestamp":1780503038000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Protective efficacy of mutant strains of\n                    <i>Borrelia burgdorferi<\/i>\n                    as potential reservoir host-targeted biologics against Lyme disease"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-6231","authenticated-orcid":true,"given":"Venkatesh","family":"Kumaresan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"South Texas Center for Emerging Infectious Diseases, Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Trever C.","family":"Smith","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"South Texas Center for Emerging Infectious Diseases, Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio","place":["San Antonio, 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