Safety/Efficacy Trial of Killed Leishmania Vaccine in Volunteers With no Response to Leishmanin

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 no response to leishmanin will be injected twice (30 days apart) with Alum-ALM 200 ug + 1/10 of BCG (n = 50) or BCG (n = 50) or BCG 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.

Conditions

• Healthy

Interventions

BIOLOGICAL

Alum-ALM + BCG

Alum precipitated autoclaved L. major

BIOLOGICAL

Alum-ALM + BCG

Arm 1=Alum-ALM + BCG Arm 2=BCG Arm 3=Placebo comparator

BIOLOGICAL

Alum-ALM + BCG

Alum-ALM + BCG

Sponsors & Collaborators

• Pasteur Institute of Iran, Tehran, Iran

  collaborator UNKNOWN

• Razi Vaccine and Serum Research Institute

  collaborator OTHER

• Centre for Disease Control & Management, Ministry of Health & Medical Education

  collaborator OTHER_GOV

• Tehran University of Medical Sciences

  lead OTHER

Principal Investigators

• Ali Khamesipour · Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences

• Farrokh Modabber · Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

16 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2007-01-31

Primary Completion

2007-05-31

Completion

2007-12-31

Countries

• Iran

Study Locations