Safety/Efficacy Trial of Killed Leishmania Vaccine in Volunteers With Positive Response to Leishmanin (LST>0)
Condition: Healthy
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Development of a safe and effective vaccine against leishmaniasis started more than 10 years
      ago under WHO/TDR supervision. An autoclaved L. major vaccine (ALM) mixed with BCG has been
      tested in human in Iran, Pakistan and Sudan. Long term follow up of the vaccinees showed no
      untoward reactions except the skin reaction at the site of injection. The efficacy results of
      ALM was not satisfactory. In order to enhance immunogenicity of the vaccine, ALM was adsorbed
      to alum (Aluminum hydroxide). Alum-ALM plus adjuvant showed to induce protection in Rhesus
      monkeys against cutaneous leishmaniasis and in Languor monkeys against visceral
      leishmaniasis. Two trials of a single injection of different doses of Alum-ALM mixed with
      1/10th of normal dose of BCG was carried out in healthy volunteers from a non endemic area of
      Sudan. The safety/immunogenicity parameters of the volunteers were closely monitored and the
      results showed that side effects were minimal and confined to the site of injection in the
      form of mild local pain, induration and ulceration, all associated with BCG vaccination. The
      immunogenicity results showed the strongest immune response seen in any Leishmania vaccine
      trials so far. It seems that this new formulation is an appropriate candidate for further
      development. Inoculation with live virulent Leishmania to produce a lesion for the purpose of
      preventing natural infection is known as leishmanization. The induced lesion heals and the
      person is usually protected against further infections. This method of prevention was
      practiced for centuries in the region. In this study volunteers with response to leishmanin
      will be injected twice (30 days apart) with Alum-ALM 200 ug + 1/10 of BCG (n = 50) or diluent
      alone (n = 50) as control. All volunteers will be leishmanized on day 60 post vaccination. In
      this trial, volunteers are protected either by vaccine or by leishmanization. The
      leishmanized volunteers will be visited by weekly and the development and healing process of
      the lesion will be monitored until complete healing of every volunteer. The immune responses
      of the volunteers will be evaluated. Vaccine efficacy is defined by the percent reduction in
      the number of volunteers developing a lesion following leishmanization as compared to
      controls on days 240.
    


Intervention name(s): Alum-ALM + BCG
Intervention type(s): Biological
Intervention description(s): Alum-ALM + BCG 200 ug per injection
Other intervention name(s): Alum pericipitated autoclaved L. major
Intervention MeSH terms: Aluminum sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Leishmaniasis vaccine; Alum-ALM; First generation vaccine; Leishmanin positive; Healthy Volunteers; Response to Leishmanin (Leishmanin Skin Test>0); No History of Cutaneous Leishmaniasis