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

Younis, B.; Osman, M.; Khalil, E.; Santoro, F.; Furini, S.; Wiggins, R.; Keding, A.; Carraro, M.; Musa, A.; Abdarahaman, M.; Mandefield, L.; Bland, M.; Aebischer, T.; Gabe, R.; Layton, A.; Lacey, C.; Kaye, P. M.

Post kala azar dermal leishmaniasis (PKDL) is a chronic, stigmatising 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 1x1010 viral particles (v.p.; adults only) or 7.5x1010 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 patients (30.4%) monitored to study completion showed >90% clinical improvement and 6 (25%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomised controlled trial to determine whether these clinical responses were vaccine related and whether ChAd63-KH vaccine has clinical utility is underway.