{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:41:09Z","timestamp":1785422469446,"version":"3.56.0"},"posted":{"date-parts":[[2025,7,10]]},"group-title":"Microbiology","reference-count":113,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["5R01AI152233"],"award-info":[{"award-number":["5R01AI152233"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32AI184340"],"award-info":[{"award-number":["T32AI184340"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lyme disease (LD), caused by\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  (\n                  <jats:italic>Bb<\/jats:italic>\n                  ), is the most common vector-borne disease in the United States. Novel strategies to control transmission of\n                  <jats:italic>Bb<\/jats:italic>\n                  to humans via ticks are critical for prevention of LD. One such strategy is to leverage non-infectious mutant strains of\n                  <jats:italic>Bb<\/jats:italic>\n                  for pathogen-derived biologics to block\n                  <jats:italic>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 (\u0394\n                  <jats:italic>badR<\/jats:italic>\n                  ) and replacement of 8 conserved residues with alanines in Carbon Storage Regulator A of\n                  <jats:italic>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>Bb<\/jats:italic>\n                  acquisition by na\u00efve\n                  <jats:italic>Ixodes scapularis<\/jats:italic>\n                  larvae following needle challenge with\n                  <jats:italic>Bb<\/jats:italic>\n                  B31-A3. While vaccination with \u0394\n                  <jats:italic>badR<\/jats:italic>\n                  mutant conferred 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>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>Bb<\/jats:italic>\n                  by na\u00efve larvae from reservoir hosts, disrupting the enzootic transmission cycle of the agent of Lyme disease.\n                <\/jats:p>","DOI":"10.1101\/2025.07.09.663885","type":"posted-content","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T22:40:11Z","timestamp":1752187211000},"source":"Crossref","is-referenced-by-count":1,"title":["Protective efficacy of mutant strains of\n                  <i>Borrelia burgdorferi<\/i>\n                  as potential reservoir host-targeted biologics against Lyme disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-6231","authenticated-orcid":false,"given":"Venkatesh","family":"Kumaresan","sequence":"first","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Molecular 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TX-78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-122X","authenticated-orcid":false,"given":"Jolie F.","family":"Starling-Lin","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio San Antonio, TX-78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Horn","sequence":"additional","affiliation":[{"name":"Bay Area Lyme Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-2435","authenticated-orcid":false,"given":"J.","family":"Seshu","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio San Antonio, 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