Department of Clinical Pathology & Immunology, Institute of Endemic Diseases, University of Khartoum, Army Ave., Khartoum, Sudan.
York Biomedical Research Institute, Hull York Medical School, University of York, Heslington, York YO10 5DD, UK.
Mol Ther. 2021 Jul 7;29(7):2366-2377. doi: 10.1016/j.ymthe.2021.03.020. Epub 2021 Mar 27.
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 × 10 viral particles (v.p.; adults only) or 7.5 × 10 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.
Post-kala-azar dermal leishmaniasis (PKDL) 是一种慢性、致盲性皮肤疾病，常发生于内脏利什曼病临床治愈后。鉴于迫切需要新的治疗方法，我们在苏丹持续性 PKDL 患者中开展了 ChAd63-KH 疫苗的 IIa 期安全性和免疫原性试验。LEISH2a（ClinicalTrials.gov：NCT02894008）是一项开放性三阶段临床试验，纳入了 16 例成年和 8 例青少年持续性 PKDL 患者（中位持续时间 30 个月；范围 6-180 个月）。患者接受单次肌肉注射 1×10 病毒颗粒（v.p.；仅用于成人）或 7.5×10 v.p.（成人和青少年），主要终点为 42-120 天随访期内的安全性，次要终点为临床反应和免疫原性。在最后一次就诊时，如果患者仍有大量疾病，将给予两性霉素 B 脂质体。ChAd63-KH 疫苗在 PKDL 患者中表现出轻微的不良反应，并通过全血转录组学和 ELISpot 检测到了强大的固有和细胞介导的免疫反应。23 例患者中有 7 例（30.4%）在监测到研究完成时显示>90%的临床改善，5 例（21.7%）显示部分改善。应用于血液转录组学数据的逻辑回归模型确定了可预测>90%临床改善患者的免疫模块。一项旨在确定这些临床反应是否与疫苗相关以及 ChAd63-KH 疫苗是否具有临床实用性的随机对照试验正在进行中。
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