{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:56:51Z","timestamp":1788947811537,"version":"build-2803163510"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>There are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole-cell vaccine approach using<jats:named-content content-type=\"genus-species\">Leishmania infantum chagasi<\/jats:named-content>promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results in<jats:named-content content-type=\"genus-species\">Leishmania<\/jats:named-content>organisms termed killed but metabolically active (KBMA). In this report, we characterize the<jats:italic>in vitro<\/jats:italic>growth characteristics of both KBMA<jats:named-content content-type=\"genus-species\">L. major<\/jats:named-content>and KBMA<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>, KBMA<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>parasites were able to initially enter liver cells<jats:italic>in vivo<\/jats:italic>after intravenous infection. However, whereas live<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>infection leads to hepatosplenomegaly in mice after 6 months, KBMA<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>parasites were undetectable in the organs of mice at this time point.<jats:italic>In vitro<\/jats:italic>, KBMA<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>or KBMA<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>displayed similar cytokine patterns<jats:italic>in vitro<\/jats:italic>. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan<jats:named-content content-type=\"genus-species\">L. infantum chagasi<\/jats:named-content>. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens.<\/jats:p>","DOI":"10.1128\/cvi.05660-11","type":"journal-article","created":{"date-parts":[[2012,2,9]],"date-time":"2012-02-09T12:05:15Z","timestamp":1328789115000},"page":"490-498","source":"Crossref","is-referenced-by-count":29,"title":["Killed but Metabolically Active Leishmania infantum as a Novel Whole-Cell Vaccine for Visceral Leishmaniasis"],"prefix":"10.1128","volume":"19","author":[{"given":"Kevin W.","family":"Bruhn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Birnbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Haskell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Vanchinathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Greger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupa","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Lin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu Anh","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Hickerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Beverley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Craft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2012,2,8]]},"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.05660-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:46:43Z","timestamp":1627591603000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.05660-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,8]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,3,28]]},"published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1128\/CVI.05660-11"],"URL":"https:\/\/doi.org\/10.1128\/cvi.05660-11","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,8]]}}}