New Vaccine/Antitoxin May Defeat Anthrax

LA JOLLA, Calif., Oct. 5 -- A single injection provided both protection against and treatment for anthrax in rats.

A "viral nanoparticle," created using an insect virus, protected against a deadly challenge with the anthrax lethal toxin, according to Anette Schneemann, Ph.D., of the Scripps Research Institute here, and colleagues.

And when the particle was combined with anthrax protective antigen -- the basis of the currently approved vaccine -- a single dose produced a robust immune response and protected the animals against death from anthrax, the researchers reported online in PLoS Pathogens.

"While other strategies are being pursued to develop improved anthrax vaccines," Dr. Schneemann said, "none of these offer the distinct advantage of combining the function of a vaccine with a potent antitoxin."

There is only one anthrax vaccine approved in the U.S., anthrax vaccine adsorbed (AVA or Biothrax), although others are under development. One disadvantage of the current vaccine, Dr. Schneemann said, is that it takes several inoculations to produce immunity.

Anthrax uses its so-called protective antigen to bind to human cells, mainly to the cellular receptor ANTXR2 at what is called the von Willebrand A domain, the researchers noted.

So they took advantage of the structure of the insect Flock House virus and created non-infectious virus-like particles with 180 copies of the ANTXR2 von Willebrand A domain dotted around the surface.

The idea was that the multiple copies of the Willebrand A domain would mop up anthrax and prevent it from binding to cells.

In rats, the researchers compared these chimeric virus-like particles with a purified monomeric form of the ANTXR2 von Willebrand A domain, which has previously been shown to protect against anthrax.

At a therapeutic concentration, both completely protected the animals from anthrax lethal toxin.

At a concentration 10 times lower, neither was protective, but the chimeric particles significantly extended the time until death (at P=0.0046), suggesting that the extra binding sites offered an advantage.

To create a potential vaccine, the researchers combined the chimeric particles with copies of the anthrax protective antigen. Rats were given two subcutaneous injections three weeks apart of protective antigen, the chimera-protective antigen complex, or the chimera by itself.

At the third week, rats given the complex had significantly higher levels of anthrax antibodies (at P=0.0028) than animals getting the antigen alone. There was no immune response to the chimeric particles alone.

When the rats were given anthrax lethal toxin, all but one of the animals immunized with protective antigen alone died, while all of those immunized with the complex survived, the researchers said.

In a subsequent experiment, the researchers found that even a single injection of the complex was enough to protect animals as soon as four weeks after vaccination.

The chimeric particles are expected to have a "desirable safety profile" in animals and humans, because the modified insect virus is missing much of its genetic material and cannot cause infection, the researchers said.