Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan

Brima M Younis, Mohamed Osman, Eltahir A G Khalil, Francesco Santoro, Simone Furini, Rebecca Wiggins, Ada Keding, Monica Carraro, Anas E A Musa, Mujahid A A Abdarahaman, Laura Mandefield, Martin Bland, Toni Aebischer, Rhian Gabe, Alison M Layton, Charles J N Lacey, Paul M Kaye, Ahmed M Musa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 ( 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.

Original languageEnglish
Pages (from-to)2366-2377
Number of pages12
JournalMolecular therapy
Issue number7
Publication statusPublished - 7 Jul 2021

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Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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