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Potential vaccine developed for deadly leishmaniasis disease

April 24, 2006

Development of a fundamentally new "candidate," or potential, vaccine for visceral leishmaniasis (LEASH-ma-NIGH-a-sis), a parasitic disease that kills about 60,000 people annually, is reported in the current issue of ACS Chemical Biology. Spread by the bite of infected female sand flies, visceral leishmaniasis infects about 500,000 people annually, with the majority of cases occurring in India, Bangladesh, Nepal, Sudan and Brazil.

Despite a major research thrust by the World Health Organization (WHO), no effective vaccine exists for the visceral, or internal, form of leishmaniasis. A milder form of leishmaniasis, which infects the skin, was reported among American military personnel during Operation Desert Storm and other conflicts in the region.

Peter H. Seeberger, Ph.D., of the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zurich headed the research group. It also included researchers from the Swiss Tropical Institute in Basel and Pevion Inc., a biotech company focusing on virosomal delivery systems. The group reported their findings in ACS Chemical Biology, one of 34 peer-reviewed journals published by the American Chemical Society, the world's largest scientific society.

Several leishmaniasis candidate vaccines are in various stages of development. Seeberger's group, however, reported development of a unique two-part preparation. It is among a new genre of carbohydrate-based vaccines stirring excitement in medical circles. Carbohydrates are chemical compounds that include sugar and are made from units linked together like beads on a chain.

"This is the first and only carbohydrate vaccine candidate against this disease," Seeberger stated. "This candidate vaccine brings something new to the table and may be of use not only in humans but also for pet vaccines. Dogs get leishmaniasis, particularly in Southern Europe and a vaccine is urgently needed there, as well."

Carbohydrate vaccines already are used in everyday medicine, including vaccines to immunize against meningitis and other bacterial infections, mainly in small children in the United States. Those vaccines use carbohydrates isolated from the actual bacteria responsible for the diseases. The carbohydrates act as antigens, which stimulate the immune system to deploy a protective shield against disease.

"Right now there is a major push to utilize synthetic carbohydrates as antigens in order to control the purity and composition and avoid possible contamination," Seeberger explained. His own group, together with a biotech company - Ancora Pharmaceuticals in Medford, Mass. - is working on one such malaria vaccine that is in late-stage preclinical trials. Other candidate vaccines against anthrax and tuberculosis are at an earlier stage of development.

One major drawback with carbohydrate vaccines is the difficulty in getting them to produce a strong immune response. Vaccine manufacturers achieve this by adding a booster substance - an adjuvant. The standard existing adjuvant, alum, has limitations. Potential alternative adjuvants are toxic, expensive or have other problems.

Seeberger's candidate vaccine combines the delivery vehicle, immune-stimulating antigen and adjuvant into one package.

The delivery vehicle is an influenza virosome - the empty envelope of the influenza virus. These flu virus shells contain none of the infectious genetic material in full-fledges flu viruses. The virosome also acts as an "adjuvant," boosting the immune response of the candidate vaccine. The antigen is a synthetic carbohydrate similar to substances on the surface of the leishmaniasis bacteria.

With laboratory studies showing that the candidate vaccine produces a strong protective action against leishmaniasis, Seeberger's group is moving on to the next step toward a leishmaniasis vaccine - tests in animals.

"To date, carbohydrates have not been used on this delivery platform," Seeberger said. "Therefore, this is a proof-of-principle study that will be applicable to many carbohydrate antigens of importance in other diseases as well," he said. Seeberger cited both infectious and parasitic diseases and vaccines against cancer.

WHO assigned a high priority to development of a leishmaniasis vaccine because of the huge human toll and the lack of any effective treatment. The most common drugs used to treat leishmaniasis have serious side effects and are expensive.

Symptoms of visceral leishmaniasis include fever, weight loss, and abnormalities of the liver and spleen.

American Chemical Society