{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:39:05Z","timestamp":1791527945536,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012155","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Leptospirosis is the most widespread zoonosis and a life-threatening disease in humans and animals. Licensed killed whole-cell vaccines are available for animals; however, they do not offer heterologous protection, do not induce long-term protection, or prevent renal colonization. In this study, we characterized an immunogenic <jats:italic>Leptospira<\/jats:italic> methyl-accepting chemotaxis protein (MCP) identified through a reverse vaccinology approach, predicted its structure, and tested the protective efficacy of a recombinant MCP fragment in the C3H\/HeJ mice model. The predicted structure of the full-length MCP revealed an architecture typical for topology class I MCPs. A single dose of MCP vaccine elicited a significant IgG antibody response in immunized mice compared to controls (<jats:italic>P<\/jats:italic> &lt; 0.0001), especially the IgG1 and IgG2a subclasses. The vaccination with MCP, despite eliciting a robust immune response, did not protect mice from disease and renal colonization. However, survival curves significantly differed between groups, and the MCP-vaccinated group developed clinical signs faster than the control group. There were differences in gross and histopathological changes between the MCP-vaccinated and control groups. The factors leading to enhanced disease process in vaccinated animals need further investigation. We speculate that anti-MCP antibodies may block the MCP signaling cascade and may limit chemotaxis, preventing <jats:italic>Leptospira<\/jats:italic> from reaching its destination, but facilitating its maintenance and replication in the blood stream. Such a phenomenon may exist in endemic areas where humans are highly exposed to <jats:italic>Leptospira<\/jats:italic> antigens, and the presence of antibodies might lead to disease enhancement. The role of this protein in <jats:italic>Leptospira<\/jats:italic> pathogenesis should be further evaluated to comprehend the lack of protection and potential exacerbation of the disease process. The absence of immune correlates of protection from <jats:italic>Leptospira<\/jats:italic> infection is still a major limitation of this field and efforts to gather this knowledge are needed.<\/jats:p>","DOI":"10.1371\/journal.pntd.0012155","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T17:37:27Z","timestamp":1727113047000},"page":"e0012155","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhancement of clinical signs in C3H\/HeJ mice vaccinated with a highly immunogenic Leptospira methyl-accepting chemotaxis protein following challenge"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-0309","authenticated-orcid":true,"given":"Liana Nunes","family":"Barbosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"LIanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha","family":"Madesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryanna Nicole","family":"Fayne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalvis","family":"Brangulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Linn-Peirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6600-9102","authenticated-orcid":true,"given":"Sreekumari","family":"Rajeev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"issue":"9","key":"pntd.0012155.ref001","doi-asserted-by":"crossref","first-page":"e0003898","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global Morbidity and Mortality of Leptospirosis: A Systematic Review","volume":"9","author":"F Costa","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"pntd.0012155.ref002","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","article-title":"Leptospirosis: a zoonotic disease of global importance","volume":"3","author":"AR Bharti","year":"2003","journal-title":"Lancet Infect Dis"},{"key":"pntd.0012155.ref003","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"DA Haake","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"issue":"2","key":"pntd.0012155.ref004","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","article-title":"Leptospirosis","volume":"14","author":"PN Levett","year":"2001","journal-title":"Clin Microbiol Rev"},{"issue":"Supplement 5","key":"pntd.0012155.ref005","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/ndt\/16.suppl_5.73","article-title":"Leptospirosis renal disease","volume":"16","author":"C-W Yang","year":"2001","journal-title":"Nephrology Dialysis Transplantation"},{"issue":"10","key":"pntd.0012155.ref006","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrmicro2208","article-title":"Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen","volume":"7","author":"AI Ko","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"pntd.0012155.ref007","unstructured":"Croda J. 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