Younis, B. M., Osman, M., Khalil, E. A. G., Santoro, F., Furini, S., Wiggins, R., Keding, A., Carraro, M., Musa, A. E. A., Abdarahaman, M. A. A., Mandefield, L., Bland, M., Aebischer, T., Gabe, R., Layton, A. M., Lacey, C. J. N., Kaye, P. M., & Musa, A. M. (2021). Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan. Molecular therapy : the journal of the American Society of Gene Therapy, 29(7), 2366–2377. https://doi.org/10.1016/j.ymthe.2021.03.020
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 X 1010 viral particles (v.p.; adults only) or 7.5 X 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.