Antibodies Shown to Counter Tularemia Bacteria

By Chris Schneidmiller
Global Security Newswire

WASHINGTON — Researchers in New York state have shown for the first time that antibodies could provide protection against the bacteria that cause tularemia, a highly infectious disease that has been identified as a possible bioterror agent (see GSN, Feb. 21).

Mice used in laboratory testing remained healthy even if they were injected with antibodies up to 48 hours after exposure to the bacteria, scientists at Albany Medical College reported in the July 1 edition of The Journal of Immunology.  “This is pretty exciting,” said lead researcher Dennis Metzger.

Tularemia is an animal disease that can spread to humans through several routes, including inhalation of the bacteria Francisella tularensis.  The Centers for Disease Control and Prevention designates the disease as a Category A bioterrorism agent — the handful of others include known killers such as anthrax, smallpox and plague.  Without treatment, the inhalational form of the disease could kill up to 30 percent of those infected.

“The main thing about it that makes it such a concern is that it’s extremely infectious and it has the potential for very serious respiratory illness in people,” said Sam Perdue, a program officer with the National Institute of Allergy and Infectious Diseases.  “It’s also available in nature, so you can get your hands on it.”

Japanese germ warfare units studied the disease in Manchuria from 1932 to 1945; Western nations also conducted research during World War II, and the United States and Soviet Union weaponized tularemia during the Cold War, according to a 2001 article in the Journal of the American Medical Association.

The World Health Organization reported in 1969 that the release of 50 kilograms of aerosolized tularemia bacteria over an urban area of 5 million people would kill 19,000 and incapacitate more than 200,000, the JAMA article stated.  Perdue noted, though, that devising an aerosol device would require a level of technical sophistication likely to be beyond that of the average individual.

There is currently no licensed vaccine for tularemia; infection would be treated with antibiotics.

The Albany Medical College project began about five years ago, after the National Institutes of Health called for increased research on potential agents of biological terrorism, Metzger said.  The school received a NIAID grant of more than $8 million to conduct multiple projects on tularemia.

Researchers infected mice with nonlethal levels of tularemia bacteria, causing the animals to produce antibodies — proteins created by the immune system to disable microbes or other foreign materials that enter the body.  They collected antibodies from the blood stream of the mice, and then injected them within a serum into other mice.

Test mice survived lethal doses of tularemia bacteria if they were given the serum before exposure, or even 24 to 48 hours afterward.  Mice that received a serum with no antibodies died after infection.

This is the first evidence that antibodies could be used fight tularemia infection in humans, Perdue said.  Some in the scientific community have previously argued that they would not offer such protection, he said.

There are a large number of people who have survived natural exposure to tularemia, and are still carrying antibodies even years later that could be used to treat victims of an attack, Metzger said.  Ultimately, white blood cells from those people could be collected and used to continuously produce “unlimited quantities” of stable antibodies, he said.

Using tularemia-specific antibodies to treat infected humans could have specific benefits in comparison to a vaccine or antibiotics.  The first is the rapid rate at which the treatment would take effect, Metzger said:  “We inject the antibodies and they go to work right away.”

The antibody serum could also be administered to patients with suppressed immune systems, such as people with AIDS or who are undergoing chemotherapy.  Vaccines often are not effective in those cases, as the shots are trying to activate an immune system that is too impaired to respond, Metzger said.

“The antibodies will work even in people that don’t have an immune system,” he said.  “Basically what we’re doing is we’re replacing their immune system with an active immune system from another person or animal.”

Increased use of antibiotics to fight a disease causes the bacteria to become increasingly resistant to that treatment, Metzger said.  Antibodies are much less likely to produce that result.

The Albany team has one more year of funding, and has applied for a five-year renewal.  Metzger said he anticipates several years of further animal study as the group seeks to better understand how the protection occurs and under what conditions.  That could be followed by clinical testing.

It was not immediately clear what regulatory approval would be required for an antibody serum to be placed into the U.S. stockpile, or the full timeline for such an initiative.

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