Safety, immunogenicity, and efficacy of a gentamicin-attenuated Leishmania major vaccine in an open-label clinical vaccine trial

An attenuated line of Leishmania major was generated by culturing promastigotes in vitro in the presence of gentamicin. Preclinical studies demonstrated that this strain was safe and capable of inducing cellular immunity. The present study evaluated the safety and immunogenicity of the gentamicin-attenuated L. major (GALM) vaccine in 27 human subjects. Safety was assessed through adverse event monitoring over a two-year follow-up, and hematological and biochemical parameters were measured at baseline and three months post-vaccination. The GALM vaccine was well tolerated, with no serious adverse events reported. All vaccinated subjects developed anti-Leishmania IgG antibodies, with significantly higher mean levels observed in males than females (P < 0.05), and exhibited a positive leishmanin skin test (≥5 mm) at 48 hours. Vaccination modulated TLR2, TLR4, and TLR9 expression in stimulated peripheral blood mononuclear cells and significantly increased IL-12 and IFN-γ secretion (P < 0.0001). For efficacy assessment, 25 subjects were challenged with wild-type L. major six months post-vaccination; only two (8%) developed lesions. One developed a self-healing lesion lasting 50 days, while the other developed a lesion 550 days post-challenge that resolved within 60 days. Overall, the GALM vaccine was safe, highly immunogenic, and conferred 92% protective efficacy against clinical infection. WHO | Iranian Registry of Clinical Trials (IRCT): (IRCT20151019024604N4).