{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:06:26Z","timestamp":1791511586662,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012707","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["RTC-2014-1767-1"],"award-info":[{"award-number":["RTC-2014-1767-1"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Canine leishmaniasis is a vectorial zoonotic disease caused by the obligate intracellular trypanosomatid parasite\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    . This chronic disease is characterized by a variable combination of cutaneous and visceral clinical signs. Despite the availability of insecticides and first-line drug therapies, prevalence remains high in many areas fundamentally distributed in the Mediterranean basin and Brazil. The development of a vaccine against leishmaniasis is a challenging objective in veterinary medicine due to the parasite\u2019s life cycle complexity, resistance, relapses, and toxicity of the currently available drugs. Vaccination against canine leishmaniasis intends to decrease the parasite burden and the risk of clinical disease. Neoleish is a third generation DNA vaccine based on the\n                    <jats:italic>L. infantum<\/jats:italic>\n                    LACK gene encoding the 36\u2009kDa protein, analogue of the receptor of the activated protein kinase C (LACK\/p36) included in the antibiotic resistance-free plasmid pPAL. Once safety and efficacy of this intranasally delivered vaccine was confirmed in the preclinical phase, this randomized double-blind field trial was performed to assess safety and efficacy of the Neoleish vaccine. It was assessed by exposing 361 healthy na\u00efve dogs to natural\n                    <jats:italic>L. infantum<\/jats:italic>\n                    infection during two consecutive transmission seasons in three endemic areas of Spain. 361 dogs were randomly split into two treatment groups (181 vaccinated and 180 placebo). The primary safety endpoint was the absence of serious local and\/or systemic adverse events and\/or deaths attributable to vaccination. Neoleish demonstrated a high safety profile. No signs of shock, local or systemic reactions were observed even after the administration of an overdose (10x) of Neoleish followed by a repeated dose. The absence of Neoleish interference with the ELISA and IFAT serological tests was confirmed after repeated vaccination. Regarding efficacy, Neoleish vaccine affected the progression of parasite multiplication in bone marrow and peripheral blood, showing a statistically significant reduction of parasite load in vaccinated animals at the end of the study. In summary, the contributions of Neoleish, a vaccine with a very high safety profile, to canine leishmaniasis prevention are: i) The odds-ratio for detectable parasites in blood is 3.5 for vaccinated dogs compared to non-vaccinated dogs; if detected, ~86% lower parasitemia levels are expected; ii) A vaccinated dog has a 2-fold lower risk of developing active infection compared to a non-vaccinated dog; in case positive, the parasite load in bone marrow is expected to be ~96% lower; iii) A 3-fold lower risk (~72.7%) of developing clinical disease is expected in a vaccinated compared to a non-vaccinated dog.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0012707","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T18:40:16Z","timestamp":1762195216000},"page":"e0012707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Large-scale randomized double-blind 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