dc.contributor.advisor | Creative Commons Attribution (CC BY 4.0) | |
dc.contributor.author | Younis, BM | |
dc.contributor.author | Osman, M | |
dc.contributor.author | Khalil, EAG | |
dc.contributor.author | Santoro, F | |
dc.contributor.author | Furini, S | |
dc.contributor.author | Wiggins, R | |
dc.contributor.author | Keding, A | |
dc.contributor.author | Carraro, M | |
dc.contributor.author | Musa, AEA | |
dc.contributor.author | Abdarahaman, MAA | |
dc.contributor.author | Mandefield, L | |
dc.contributor.author | Bland, M | |
dc.contributor.author | Aebischer, T | |
dc.contributor.author | Gabe, R | |
dc.contributor.author | Layton, AM | |
dc.contributor.author | Lacey, CJN | |
dc.contributor.author | Kaye, PM | |
dc.contributor.author | Musa, AM | |
dc.date.accessioned | 2021-04-26T17:43:40Z | |
dc.date.available | 2021-03-23 | |
dc.date.available | 2021-04-26T17:43:40Z | |
dc.date.issued | 2021-03-27 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/71499 | |
dc.description.abstract | Post-kala-azar dermal leishmaniasis (PKDL) is a chronic, stigmatizing skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (ClinicalTrials.gov: NCT02894008) was an open-label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration, 30 months; range, 6-180 months). Patients received a single intramuscular vaccination of 1 × 1010 viral particles (v.p.; adults only) or 7.5 × 1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow-up. AmBisome was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot. 7/23 patients (30.4%) monitored to study completion showed >90% clinical improvement, and 5/23 (21.7%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomized controlled trial to determine whether these clinical responses were vaccine-related and whether ChAd63-KH vaccine has clinical utility is underway. | en_US |
dc.language | eng | |
dc.relation.ispartof | Molecular Therapy | |
dc.subject | ChAd63-KH vaccine | en_US |
dc.subject | PKDL | en_US |
dc.subject | Sudan | en_US |
dc.subject | clinical trial | en_US |
dc.subject | immunogenicity | en_US |
dc.subject | leishmaniasis | en_US |
dc.subject | safety | en_US |
dc.subject | transcriptomics | en_US |
dc.title | Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan. | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2021 The Author(s). | |
dc.identifier.doi | 10.1016/j.ymthe.2021.03.020 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/33781913 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2021-03-23 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |