Safety, immunogenicity, and efficacy of a gentamicin-attenuated Leishmania major vaccine in an open-label clinical vaccine trial

Safety, immunogenicity, and efficacy of a gentamicin-attenuated Leishmania major vaccine in an open-label clinical vaccine trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Safety, immunogenicity, and efficacy of a gentamicin-attenuated Leishmania major vaccine in an open-label clinical vaccine trial Hamid Daneshvar, Ali Akbar Haghdoost, Alireza Keyhani, Zeynab Fallah Zohabi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8779695/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract An attenuated line of Leishmania major was generated by culturing promastigotes in vitro in the presence of gentamicin. Preclinical studies demonstrated that this strain was safe and capable of inducing cellular immunity. The present study evaluated the safety and immunogenicity of the gentamicin-attenuated L. major (GALM) vaccine in 27 human subjects. Safety was assessed through adverse event monitoring over a two-year follow-up, and hematological and biochemical parameters were measured at baseline and three months post-vaccination. The GALM vaccine was well tolerated, with no serious adverse events reported. All vaccinated subjects developed anti-Leishmania IgG antibodies, with significantly higher mean levels observed in males than females (P < 0.05), and exhibited a positive leishmanin skin test (≥5 mm) at 48 hours. Vaccination modulated TLR2, TLR4, and TLR9 expression in stimulated peripheral blood mononuclear cells and significantly increased IL-12 and IFN-γ secretion (P < 0.0001). For efficacy assessment, 25 subjects were challenged with wild-type L. major six months post-vaccination; only two (8%) developed lesions. One developed a self-healing lesion lasting 50 days, while the other developed a lesion 550 days post-challenge that resolved within 60 days. Overall, the GALM vaccine was safe, highly immunogenic, and conferred 92% protective efficacy against clinical infection. WHO | Iranian Registry of Clinical Trials (IRCT): (IRCT20151019024604N4). Health sciences/Diseases Biological sciences/Immunology Health sciences/Medical research Biological sciences/Microbiology Leishmania Vaccine Gentamicin-attenuated parasite Leishmanization Cutaneous leishmaniasis Clinical trial phase I Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8779695","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":617496256,"identity":"c5839dbd-37b7-4844-86d9-78ffe653e19e","order_by":0,"name":"Hamid Daneshvar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYBACA4YEEHUAiPmff/5hYANkMDYeIFILDxszQ0UaSEsDKVrOHGaAcXECc/bkZw8+/LmT2D/77LHHhW3n7da2HwbaUmMTjUuLZc8zc8OZbc8SZ5zLSzee2XY7eduZRKCWY2m5DbgcdiPBTJq34bAxwxkGAwleoBazA0AtjA2H8WhJ/yb9589hY3mIlnPJZucfEtKSYybNwHZYzuAMj5k0z5kDdmY3CNly5k2ZZG/bYTnDM2zJhjMqkhPMbgBtScDnl+Pp2yR+/DnMI3eG+eCDDwZ29mbn0x8++FBjg1MLBkgEq0wgVjkI2JOieBSMglEwCkYGAAB2c2xP2wJFJwAAAABJRU5ErkJggg==","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Hamid","middleName":"","lastName":"Daneshvar","suffix":""},{"id":617496259,"identity":"18e6d2dd-c34e-4480-9321-e64bc81417a1","order_by":1,"name":"Ali Akbar Haghdoost","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"Akbar","lastName":"Haghdoost","suffix":""},{"id":617496260,"identity":"df3f2283-3dab-43ee-a283-0e01abd5d433","order_by":2,"name":"Alireza Keyhani","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Alireza","middleName":"","lastName":"Keyhani","suffix":""},{"id":617496262,"identity":"f5f72bcb-3188-4877-8247-16187cbe1d1b","order_by":3,"name":"Zeynab Fallah Zohabi","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zeynab","middleName":"Fallah","lastName":"Zohabi","suffix":""}],"badges":[],"createdAt":"2026-02-03 20:23:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8779695/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8779695/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109296647,"identity":"a7e5eafa-5fcd-47fa-8a9f-8267b653f0c1","added_by":"auto","created_at":"2026-05-15 08:48:56","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":425692,"visible":true,"origin":"","legend":"","description":"","filename":"ManSciefinal..pdf","url":"https://assets-eu.researchsquare.com/files/rs-8779695/v1_covered_e70e64f7-c166-410b-a375-9e3488b1d2eb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety, immunogenicity, and efficacy of a gentamicin-attenuated Leishmania major vaccine in an open-label clinical vaccine trial","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Leishmania, Vaccine, Gentamicin-attenuated parasite, Leishmanization, Cutaneous leishmaniasis, Clinical trial phase I","lastPublishedDoi":"10.21203/rs.3.rs-8779695/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8779695/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"An attenuated line of Leishmania major was generated by culturing promastigotes in vitro in the presence of gentamicin. Preclinical studies demonstrated that this strain was safe and capable of inducing cellular immunity. The present study evaluated the safety and immunogenicity of the gentamicin-attenuated L. major (GALM) vaccine in 27 human subjects. Safety was assessed through adverse event monitoring over a two-year follow-up, and hematological and biochemical parameters were measured at baseline and three months post-vaccination. The GALM vaccine was well tolerated, with no serious adverse events reported. All vaccinated subjects developed anti-Leishmania IgG antibodies, with significantly higher mean levels observed in males than females (P \u003c 0.05), and exhibited a positive leishmanin skin test (≥5 mm) at 48 hours. Vaccination modulated TLR2, TLR4, and TLR9 expression in stimulated peripheral blood mononuclear cells and significantly increased IL-12 and IFN-γ secretion (P \u003c 0.0001). 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