Yet another anthrax monoclonal antibody treatment--highly effective in guinea pigs

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New antibody shows promise as cure for anthrax

A new anthrax antibody engineered by researchers at The University of

Texas at Austin protects and defends against inhalation anthrax without

the use of antibiotics and other more expensive antibodies.

The high-affinity antibody, an anthrax antitoxin, successfully

eliminated both anthrax bacteria and its deadly toxins in animal tests.

If future tests concur, this could be the first successful treatment

for late-stage anthrax infection, even for an anthrax strain that has

been designed to resist antibiotics.

The new antibody treatment, reported in the journal Infection and

Immunity, is the result of collaboration between the labs of Brent

Iverson and Georgiou at The University of Texas at Austin and a

research team led by at the Southwest Foundation for

Biomedical Research ( SFBR ) in San .

" What we have found is that you may not even need the antibiotics to

beat anthrax, " says Iverson. He says that the new treatment " looks

promising " and that it could lead to a simpler and cheaper way to treat

anthrax. The new antibody is produced in bacterial cells, rather than

the more expensive mammalian cell culture now used to produce anthrax

antibodies.

, at SFBR, adds, " A concern to national defense is that

terrorists might design a strain of anthrax that is resistant to

antibiotics, but this antitoxin could eliminate those concerns by

providing an effective treatment that doesn't require antibiotics. "

Anthrax infection is successfully treatable only in its early stages,

when antibiotics can be used to kill anthrax bacteria. Before 2002,

nothing was available to treat the large amounts of deadly toxin

released by those bacteria, which is what leads to death in patients

with late-stage anthrax infection.

In 2002, Iverson and Georgiou reported that their labs had developed a

high-affinity, " sticky " antibody designed to bind with anthrax toxin

and remove it from the body.

This antibody was licensed to Elusys Theraputics, a biopharmaceutical

company, who turned it into a full immunoglobulin G ( IgG ).

In trials, Elusys has found that the IgG protects test animals from

anthrax when administered both before and after exposure to the

disease.

Since those findings, Mabry of the Iverson and Georgiou

laboratory has reformulated the antitoxin to make it last longer in the

bloodstream.

Mabry also produced the antibody in bacterial culture, which could

eliminate the need for complicated and expensive IgG production in

mammalian cell culture.

and Carrión at SFBR tested the re-engineered

antibody with guinea pigs to determine if the antitoxin could protect

against a true infection with anthrax spores.

" We expected the antitoxin to extend the lifespan of the infected

animals, " says , " but since we did not couple it with

antibiotics, we thought that the bacteria would continue to replicate,

and the increasing amount of toxins would eventually overpower the

treatment. "

In fact, results differed from the scientists' expectations, leading to

the serendipitous discovery that the antibody effectively eliminates

both the toxin and the anthrax bacteria.

In two separate experiments conducted in SFBR's biosafety level 4,

maximum containment laboratory, researchers placed anthrax spores in

the nasal passages of guinea pigs, mimicking exposure to inhalation

anthrax.

The doses were 250 to 625 times what would ordinarily be lethal to 50

percent of the animals.

After 72 hours, the animals not treated with the antitoxin succumbed to

the infection, but those that received the treatment were still healthy

two and three weeks later.

" Day after day, we came into the lab to find the animals still healthy

and happy, " said.

Upon examination of all the animals at the end of both experiments,

researchers found no evidence of disease, with no or only trace amounts

of anthrax residing in typical reservoirs for the bacteria, the lungs

and spleen.

Iverson cautions it's not yet clear that this antibody treatment is as

effective as the IgG antibody produced by Elusys, and that he and his

collaborators are doing more studies to confirm that.

The researchers also plan to conduct additional tests to determine how

the antitoxin eliminates anthrax bacteria, which is still unknown. They

have two hypotheses, which might both be part of the full story.

One hypothesis is that the antitoxin somehow neutralizes anthrax

bacteria and prevents it from replicating.

The other looks to innate immunity, theorizing that since the

high-affinity antibody clears the body of the deadly toxin, it allows

the body's initial immune response to successfully kill the anthrax

bacteria on its own.

Source: University of Texas at Austin, 2005

XagenaMedicine2005

Meryl Nass, MD

Mount Desert Island Hospital

Bar Harbor, Maine 04609

207 288-5081 ext. 220