{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:00:54Z","timestamp":1790654454015,"version":"4.1.0"},"reference-count":37,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["108518"],"award-info":[{"award-number":["108518"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    The leishmaniases are neglected tropical diseases caused by various\n                    <ns3:italic>Leishmania<\/ns3:italic>\n                    parasite species transmitted by sand flies. They comprise a number of systemic and cutaneous syndromes including kala-azar (visceral leishmaniasis, VL), cutaneous leishmaniasis (CL), and post-kala-azar dermal leishmaniasis (PKDL). The leishmaniases cause significant mortality (estimated 20 - 50,000 deaths annually), morbidity, psychological sequelae, and healthcare and societal costs. Treatment modalities remain difficult. E.g., East African PKDL requires 20 days of intravenous therapy, and\u00a0frequently relapsing VL is seen in the setting of HIV and immunodeficiency. We developed a new therapeutic vaccine, ChAd63-KH for VL \/ CL \/ PKDL and showed it to be safe and immunogenic in a phase 1 trial in the UK, and in a phase 2a trial in PKDL patients in Sudan. \u00a0\u00a0\n                  <\/ns3:p>\n                  <ns3:p\/>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    This is a randomised double-blind placebo-controlled phase 2b trial to assess the therapeutic efficacy and safety of ChAd63-KH in patients with persistent PKDL in Sudan. 100 participants will be randomly assigned 1:1 to receive placebo or ChAd63-KH (7.5 x10\n                    <ns3:sup>10<\/ns3:sup>\n                    vp i.m.) at a single time point. Follow up is for 120 days after dosing and we will compare the clinical evolution of PKDL, as well as the humoral and cellular immune responses between the two arms.\n                  <\/ns3:p>\n                  <ns3:p\/>\n                  <ns3:p>\n                    <ns3:bold>Discussion:<\/ns3:bold>\n                    Successful development of a therapeutic vaccine for leishmaniasis would have wide-ranging direct and indirect healthcare benefits that could be realized rapidly. For PKDL patients, an effective therapeutic vaccination used alone \u00a0\u00a0would have very significant clinical value, reducing the need for extensive hospitalization and chemotherapy. Combining vaccine with drug (immuno-chemotherapy) might significantly increase the effective life of new drugs, with lower dose \/ abbreviated regimens helping to limit the emergence of drug resistance. If therapeutic benefit of ChAd63-KH can be shown in PKDL further evaluation of the vaccine in other forms of leishmaniasis should be considered.\n                  <\/ns3:p>\n                  <ns3:p\/>\n                  <ns3:p>\n                    <ns3:bold>Clinicaltrials.gov registration:<\/ns3:bold>\n                    NCT03969134.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.17951.1","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T08:40:49Z","timestamp":1659516049000},"page":"200","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis"],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9250-2638","authenticated-orcid":false,"given":"Charles","family":"Lacey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Musa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El Tahir","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brima","family":"Younis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Osman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Wiggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Keding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8796-4755","authenticated-orcid":false,"given":"Paul","family":"Kaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence.","volume":"7","author":"J Alvar","year":"2012","journal-title":"PloS One."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"371-372","DOI":"10.1016\/s0140-6736(09)61401-x","article-title":"East African countries struggle with visceral leishmaniasis.","volume":"374","author":"T Burki","year":"2009","journal-title":"Lancet."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1475-9292-6-7","article-title":"Consultation meeting on the development of therapeutic vaccines for post kala azar dermal leishmaniasis.","volume":"6","author":"H Ghalib","year":"2007","journal-title":"Kinetoplastid Biol Dis."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"65-74","DOI":"10.1016\/j.pt.2013.12.004","article-title":"Post kala-azar dermal leishmaniasis: an unresolved mystery.","volume":"30","author":"D Mukhopadhyay","year":"2014","journal-title":"Trends Parasitol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"708391","DOI":"10.1155\/2013\/708391","article-title":"Treatment-based strategy for the management of post-kala-azar dermal leishmaniasis patients in the Sudan.","author":"A Musa","year":"2013","journal-title":"J Trop Med."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"87-98","DOI":"10.1016\/s1473-3099(03)00517-6","article-title":"Post-kala-azar dermal leishmaniasis.","volume":"3","author":"E Zijlstra","year":"2003","journal-title":"Lancet Infect Dis."},{"key":"ref-7","first-page":"65","article-title":"World Health Assembly: first special session, Geneva, 9 November 2006: resolutions and decision: annex.","year":"2007"},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"239-253","DOI":"10.1111\/j.0105-2896.2004.00188.x","article-title":"The immunopathology of experimental visceral leishmaniasis.","volume":"201","author":"P Kaye","year":"2004","journal-title":"Immunol Rev."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"7160-7171","DOI":"10.4049\/jimmunol.174.11.7160","article-title":"Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis.","volume":"174","author":"R Basu","year":"2005","journal-title":"J Immunol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"1287-1292","DOI":"10.1038\/nm933","article-title":"Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses.","volume":"9","author":"S Stager","year":"2003","journal-title":"Nat Med."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fimmu.2012.00005","article-title":"CD8(+) T cells in leishmania infections: friends or 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experimental visceral leishmaniasis with CD8+ T cells requires the presence of cognate antigen.","volume":"74","author":"R Polley","year":"2006","journal-title":"Infect Immun."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"805-817","DOI":"10.1084\/jem.20061141","article-title":"Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis.","volume":"204","author":"S Nylen","year":"2007","journal-title":"J Exp Med."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"2567-2574","DOI":"10.1016\/j.vaccine.2006.07.035","article-title":"Viral vectors for malaria vaccine development.","volume":"25","author":"S Li","year":"2007","journal-title":"Vaccine."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"2538-2547","DOI":"10.4049\/jimmunol.171.5.2538","article-title":"Prime-boost vaccination with HIV-1 Gag protein and cytosine phosphate guanosine oligodeoxynucleotide, followed by adenovirus, 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gene expression in the transduction of peripheral blood lymphocytes and tumor-infiltrating lymphocytes.","volume":"20","author":"S Jones","year":"2009","journal-title":"Human Gene Therapy."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"370-373","DOI":"10.1111\/j.2042-7158.1988.tb05271.x","article-title":"The therapeutic effect of sodium stibogluconate in BALB\/c mice infected with Leishmania donovani is organ-dependent.","volume":"40","author":"K Carter","year":"1988","journal-title":"J Pharm Pharmacol."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"2089-2092","DOI":"10.1128\/AAC.41.10.2089","article-title":"Comparison of the efficacies of various formulations of amphotericin B against murine visceral leishmaniasis.","volume":"41","author":"A Mullen","year":"1997","journal-title":"Antimicrob Agents Chemother."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"3-26","DOI":"10.1093\/epirev\/mxj003","article-title":"Immunization to protect the US Armed Forces: heritage, current practice, and prospects.","volume":"28","author":"J Grabenstein","year":"2006","journal-title":"Epidemiol Rev."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"217-221","DOI":"10.1016\/j.jsb.2005.12.006","article-title":"Capsid-like arrays in crystals of chimpanzee adenovirus hexon.","volume":"154","author":"F Xue","year":"2006","journal-title":"J Struct Biol."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"11603-11613","DOI":"10.1128\/JVI.75.23.11603-11613.2001","article-title":"Replication-defective vector based on a chimpanzee adenovirus.","volume":"75","author":"S Farina","year":"2001","journal-title":"J Virol."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"e0005527","DOI":"10.1371\/journal.pntd.0005527","article-title":"A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: first-in-human trial of ChAd63-KH.","volume":"11","author":"M Osman","year":"2017","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"2366-2377","DOI":"10.1016\/j.ymthe.2021.03.020","article-title":"Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan.","volume":"29","author":"B Younis","year":"2021","journal-title":"Mol Ther."},{"key":"ref-28","article-title":"Leish2b - A Phase Iib Study to Assess the Safety, Efficacy and Immunogenicity of the Leishmania Vaccine Chad63-kh in Post-kala Azar Dermal Leishmaniasis.","author":"P Kaye","year":"2022"},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"563-9","DOI":"10.1179\/136485905X514127","article-title":"Efficacy of liposomal amphotericin B (AmBisome) in the treatment of persistent post-kala-azar dermal leishmaniasis (PKDL).","volume":"99","author":"A Musa","year":"2005","journal-title":"Ann Trop Med Parasitol."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"528-34","DOI":"10.4269\/ajtmh.2011.10-0683","article-title":"Economic consequences of post-kala-azar dermal leishmaniasis in a rural Bangladeshi community.","volume":"85","author":"M Ozaki","year":"2011","journal-title":"Am J Trop Med Hyg."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"e0203407","DOI":"10.1371\/journal.pone.0203407","article-title":"Knowledge, stigma, health seeking behaviour and its determinants among patients with post kalaazar dermal leishmaniasis, Bihar, India.","volume":"13","author":"P Garapati","year":"2018","journal-title":"PLoS One."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"251-258","DOI":"10.1093\/cid\/ciy891","article-title":"Quantifying the infectiousness of post-kala-azar dermal leishmaniasis toward sand flies.","volume":"69","author":"D Mondal","year":"2019","journal-title":"Clin Infect Dis."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"e0008468","DOI":"10.1371\/journal.pntd.0008468","article-title":"The potential impact of human visceral leishmaniasis vaccines on population incidence.","volume":"14","author":"E Le Rutte","year":"2020","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"e0008221","DOI":"10.1371\/journal.pntd.0008221","article-title":"Post kala-azar dermal leishmaniasis: A threat to elimination program.","volume":"14","author":"M Gedda","year":"2020","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"404-410","DOI":"10.1093\/cid\/cix808","article-title":"Monitoring of Parasite Kinetics in Indian Post-Kala-azar Dermal Leishmaniasis.","volume":"66","author":"S Moulik","year":"2018","journal-title":"Clin Infect Dis."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"102748","DOI":"10.1016\/j.ebiom.2020.102748","article-title":"Host transcriptomic signature as alternative test-of-cure in visceral leishmaniasis patients co-infected with HIV.","volume":"55","author":"W Adriaensen","year":"2020","journal-title":"EBioMedicine."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"41-54","DOI":"10.1146\/annurev-med-012621-102252","article-title":"COVID-19 Vaccines: Adenoviral Vectors.","volume":"73","author":"C Jacob-Dolan","year":"2022","journal-title":"Annu Rev Med."}],"container-title":["Wellcome Open 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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}