Seattle’s IDRI launches trial of leishmaniasis vaccine in Sudan

Seattle’s nonprofit global health research organization IDRI has launched a phase 1 trial of its leishmaniasis vaccine in Sudan.

A phase 1 trial is primarily designed to test the safety of a new drug or vaccine, although sometimes it can give an indication of how effective a new treatment is.

The vaccine targets leishmaniasis (leash’ma-NIGH-a-sis), a parasitic infection that is primarily found in tropical and subtropical parts of the developing world.

[PHOTO: Leishmaniasis parasites within a cell - Dr. Francis W. Chandler/CDC]

The parasite is spread from animals to people and from person to person by the bite of a blood-sucking sandfly.

Currently there is no effective vaccine, and most treatments are long, toxic and often ineffective.

Some new drugs are available that are more effective than traditional treatments, but these are too expensive for most people living in the developing countries where most cases of leishmaniasis occur.

Dr. Anne-Marie Beckmann, IDRI’s vice president of Vice-President Product Development and Head of Regulatory Affairs, said it is hoped that the vaccine will help make treatment shorter, cheaper and more effective by helping the immune system attack the parasites.

Designing an effective vaccine against leishmaniasis is difficult because the parasite has developed a myriad of strategies to elude the human immune counterattack, Beckmann said.

“Like many parasites, leishmaniasis has developed over the course of its evolution proteins on its surface that either isn’t seen by the immune system or, if seen, that don’t trigger a strong immune response,” Dr. Beckman said.

Sandfly - Frank Collins/CDC

The parasite also has the ability to invade and live within a person’s cells where the parasite can hide from the immune system.

The experimental IDRI vaccine contains proteins and immune-stimulating compounds, called adjuvants, that are designed to trigger a stronger immune reaction to the parasite, in particular to trigger a reaction called a “cell-mediated” immune response, Beckmann said.

Many standard vaccines work primarily by creating antibodies against the invading microbes. In general, antibodies attack microbes as they float freely in the blood and other fluids. Vaccines against hepatitis and influenza, for example, rely on an antibody-mediated response.

But antibodies aren’t effective against against microbes, like leishmaniasis, which can hide out within cells.

A cell-mediated response, on the other hand, creates immune cells that seek out and kill cells where the parasites are hiding, destroying the parasites within as well.

The IDRI vaccine is being tested against several forms of the infection. What form the infection takes depends on the type of parasite is causing the disease. Different forms of the disease predominate in different parts of the world.

One form of infection that primarily affects the skin, called cutaneous leishmaniasis, is common in countries in southwest Asia, such as Afghanistan, the Middle East, North Africa and in Brazil and Peru.

IDRI Researchers

Cutaneous leishmaniasis causes skin rashes, nodules and ulcerating sores.

IDRI’s vaccine has been tested in Brazil against this form of leishmaniasis.

Another form, called mucosal leishmaniasis, attacks the mucous membranes of the nose and mouth and can be severely disfiguring. IDRI’s vaccine has been tested in Peru against this form of leishmaniasis.

The trial just launched in Sudan will be tested against a particular skin condition that develops after someone has the third common form of the disease, called visceral leishmaniasis.

In visceral leishmaniasis, the parasites primarily attack the liver, spleen and lymph nodes.

The disease is common in southern Asia, countries like India, Bangladesh, and Nepal, and in Sudan and Brazil.

Visceral leishmaniasis is a particularly dangerous disease. Worldwide, about 500,000 people develop visceral leishmaniasis of whom ten percent will die. Most cases are children.

Visceral leishmaniasis is also called kala-azar (Hindi meaning “black fever”) because the skin of some patients take on a grayish cast.

The skin condition the IDRI vaccine will target in the Sudan trial is called called PKDL, for post kala-azar dermal leishmaniasis.

PKDL occurs because even after a person has cleared visceral leishmaniasis or kala-azar some of the parasites can find a safe haven from the immune system in the skin.

The infection not only causes a skin disease it allows the parasite to be spread by sandfly bite to others, perpetuating leishmaniasis in the community.

42 patients with persistent PKDL will be enrolled and randomly assigned to receive either the vaccine or a placebo. All the patients will be given drug treatment as well.

If the combination is successful, Beckman said, it will not only improve treatment of PKDL but could halt the spread of the parasite from person to person and possibly eliminating leishmaniasis from the region.

Results of the trial will be known in 2011.

To learn more:

• Visit the IDRI Web site.
• Visit the National Library of Medicine information page on leishmaniasis.