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New Mouse Study Method Enables Comparative Vaccine Studies for Tularemia

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News

New Mouse Study Method Enables Comparative Vaccine Studies for Tularemia

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NIAID scientists studying the bacterial disease tularemia have developed a novel study method that enables them, in the preferred mouse species, to compare immune protection components of prospective vaccines.

There is no licensed vaccine against tularemia; between 100 and 200 cases of tularemia are reported each year to the U.S. Centers for Disease Control and Prevention. Infection is usually caused by bites from ticks or flies, but the bacterium also can enter through the skin, eyes and mouth and lungs. The disease usually features high fever, skin blisters and swollen glands; its most severe form - pneumonic - includes coughing, chest pain and breathing difficulty.

Background
Scientists have focused on Francisella tularensis, the bacterium that causes tularemia, since the 1950s because it is highly infectious in small quantities and can be lethal, making it a potential biological weapon. By the 1960s, U.S. researchers had developed an experimental live vaccine (LVS). The vaccine has not been licensed for public use, however, because scientists haven’t been able to learn how it provides immune protection. Also, because the vaccine uses live bacteria that can weaken over time, protection against tularemia using this vaccine is unpredictable.

Before they can successfully develop new tularemia vaccines, scientists must understand what cellular properties are required to create immunity in candidate vaccines and vaccinated individuals.

Research Advance
Using two different strains of the experimental vaccine, scientists were able to establish variable levels of protection against a lethal dose of virulent F. tularensis in C57Bl/6 mice, the preferred model to study host immune responses. They also determined the type and quantity of immune cells required for protection, and designed a laboratory procedure to duplicate how these immune cells prevent virulent F. tularensis from replicating in a host. Finally, the researchers noted that in mice fully protected against virulent F. tularensis, immune cells from the lungs - compared to those found in other immune organs - appeared to most effectively control bacterial replication.

Significance
The research group is determining how immune cells from the lungs help protect against tularemia, potentially to specifically target these cells in the development of new vaccines. Scientists also are comparing genetic differences between the two vaccine strains to determine why one was more effective. Together these observations and tools provide new approaches to create safe and effective vaccines against tularemia.

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