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Bacteria to fight parasites

LeishmaniasisGrant to develop vaccine to rampant parasitic disease may help protect US troops, civilians, and local people in the Middle East.

Leishmaniasis is a disease caused by parasites that are transmitted by sand fly bites. The disease is widespread in 88 nations, with two million new cases annually. It is considered one of the most important emerging parasitic diseases, second only to malaria in terms of the number of affected people. Iraq and Afghanistan, where the U.S. military is on active duty, are among the nations where this disease is prevalent.

Cutaneous leishmaniasis causes skin ulcers on the face, arms and legs that leave significant scarring without treatment. The conventional drugs used to treat it are highly toxic and expensive, and the parasites are becoming resistant to typical treatments.

Dr. Hélène Marquis, associate professor of microbiology at the College of Veterinary Medicine, knew a little about leishmaniasis but she never expected she’d be working on the disease. That all changed last year when she saw request from the U.S. Department of Defense asking for researchers to develop vaccines that use the bacteria Listeria as a delivery device.

Marquis is an expert in Listeria, and the request got her thinking.

Listeria is primarily known as a food-borne microbe that has the ability to multiply in a large variety of cell types,” she explained. “But when you delete specific genes from Listeria, the bacterium loses its ability to cause disease. At the same time, it still triggers a strong immune response. That’s why it is commonly used as a delivery system for experimental vaccines.

“Interestingly, the requirements for the development of a robust and long-lasting protective immunity against Listeria are the same as the requirements for protection against leishmaniasis.”

So Marquis proposed to generate Listeria-based vaccines that express antigens to protect against leishmaniasis. To do this, she partnered with Susana Mendez, assistant professor of immunology and infectious diseases at Cornell’s Baker Institute for Animal Health and an expert in leishmaniasis, and Jesus Valenzuela, chief of the vector molecular biology section at the National Institute of Allergy and Infectious Diseases.

Together they received a $630,000, three-year grant from the Department of Defense’s Congressional-Directed Research Program. Valenzuela and Mendez had previously reported that vaccinating mice against specific sand fly salivary gland proteins protects against cutaneous leishmaniasis. The goal of the proposal is to improve the efficacy and duration of immunity against these sandfly salivary gland proteins using Listeria as a delivery device for the vaccine.

 “If we are successful, there is the potential of translating our results into the development of human vaccines that will serve to protect our military in endemic regions, civilians traveling to these areas, as well as individuals living in countries where the disease is endemic,” Marquis said.