{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:00:42Z","timestamp":1790654442290,"version":"4.1.0"},"reference-count":233,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo State Research Foundation","award":["FAPESP 2023\/01641-1"],"award-info":[{"award-number":["FAPESP 2023\/01641-1"]}]},{"name":"LIM50-FMUSP"},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Leishmaniasis is an infectious disease caused by several species of Leishmania parasites that preferentially infect macrophages as host cells. These intracellular parasites can evade the main microbicidal effector mechanisms of phagocytic cells and, in turn, are able to stimulate marked Th2 or regulatory T cell immune responses, which are not protective for the host. The presence of a non-protective immune response, together with the multiplication and spread of Leishmania parasites throughout the tissues, leads to the main clinical forms of leishmaniasis, such as cutaneous and visceral leishmaniasis. Although some clinical forms can be reproduced in experimental hosts such as mice and hamsters, these models do not fully mimic natural infection, which, in fact, impacts experimental vaccine development. For example, BALB\/c mice are generally infected with around one million parasites, whereas humans are not infected with more than 1000 parasites, together with vector saliva. This excessive number of parasites in experimental models may affect the efficacy of vaccines in preclinical studies. Indeed, many experimental studies conducted over the past 20 years have shown only partial protection, regardless of the vaccine generation, host species employed, or the use of adjuvants. This review aims to summarize the main aspects associated with Leishmania vaccine development, including parasite diversity, host factors, immune responses, adjuvants, and antigens. Although many elegant studies have been conducted, it is possible that some essential step is still missing for the development of an effective vaccine for human use.<\/jats:p>","DOI":"10.3390\/vaccines14010054","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Overview of the Factors Related to Leishmania Vaccine Development"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-6381","authenticated-orcid":false,"given":"Luiz Felipe Domingues","family":"Passero","sequence":"first","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, Brazil"},{"name":"Institute for Advanced Studies of Ocean (IEAMAR), S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4462-1952","authenticated-orcid":false,"given":"Italo Novais","family":"Cavallone","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, Brazil"},{"name":"Institute for Advanced Studies of Ocean (IEAMAR), S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, Brazil"},{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-7298","authenticated-orcid":false,"given":"Gabriela Venicia","family":"Ara\u00fajo Flores","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, Brazil"},{"name":"Institute for Advanced Studies of Ocean (IEAMAR), S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, Brazil"},{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-2509","authenticated-orcid":false,"given":"Sarah Santos","family":"de Lima Melchert","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, Brazil"},{"name":"Institute for Advanced Studies of Ocean (IEAMAR), S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, Brazil"},{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-2440","authenticated-orcid":false,"given":"M\u00e1rcia Dalastra","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, September 30). 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