ChAd63-KH(The University of York)

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.

Leishmaniasis is considered as a zoonotic infection and neglected tropical disease. Leishmania treatment is not totally successful and imposes high expenditures, especially in developing countries. Since the natural infection leads to the robust immunity in most of the human cases, many bodies of research have been focusing on Leishmania vaccines, being capable to control Leishmania infection. First generation vaccines (such as Leishmune^® and CaniLeish^®) have proved robust protective immunity in dogs. In human, recombinant vaccines, including Leish-F1 could confer some degrees of protective immunity against natural infection. Recently, ChAd63-KH DNA vaccine has been accomplished in providing prevention against Leishmania infection; however, this vaccine should be further evaluated in other clinical trials.