RxPG News : Anthrax

Monoclonal antibody recognizes a specific sugar on the surface of anthrax bacteria spores

Fri, 18 Aug 2006 18:46:37 PST

( from http://www.rxpgnews.com ) Spores of the dreaded Bacillus anthracis have already been used as a bioweapon against the civilian population. Once inhaled, the anthrax pathogen almost always leads to death if the victims are not treated within 24 to 48 hours. Rapid and accurate diagnosis is thus vital. A team from the Swiss Federal Institute of Technology (ETH) in Zürich, the Swiss Tropical Institute, and the University of Bern has now developed a new immunological approach that can be used to specifically recognize anthrax spores.

A number of tests for the diagnosis of anthrax already exist, including some highly accurate but also extremely complex, time-consuming, and expensive genetic methods. In contrast, immunological tests are very simple; however, it has not yet been possible to develop a truly reliable immunoassay. The similarity of the anthrax spore surface to the spores of other bacteria that commonly occur in humans has been a major problem: previous anthrax antibodies were not sufficiently specific.

Some time ago, a special carbohydrate consisting of four sugar components was discovered on the surface of anthrax spores. This carbohydrate contains a sugar component that occurs nowhere else and has been named anthrose. Peter H. Seeberger and his team targeted this carbohydrate as their point of attack.

In order to produce antibodies against a molecule, one first needs a large enough amount of the molecule in question, or antigen. However, it is exceptionally difficult to isolate a carbohydrate bound to the surface of a cell in its pure form. Seeberger and his team thus chose an alternative route: they synthesized the carbohydrate in the laboratory, attached it to a special "carrier" protein and injected this compound into mice. The carrier protein stimulated an immunological reaction, which is normally rather weak for carbohydrate antigens. The researchers were then able to obtain monoclonal antibodies from these immunized mice. These antibodies were found to bind very specifically to anthrax spores; in contrast, they do not react to bacteria closely related to Bacillus anthracis. "Our results demonstrate that small differences in the carbohydrates on cell surfaces can be used to obtain specific immune reagents," says Seeberger. "Our new antibodies will be used as the basis for highly sensitive anthrax diagnosis and will contribute to the development of new therapeutic approaches."

Scientists design functionalized liposome - a potent anthrax toxin inhibitor

Tue, 25 Apr 2006 21:19:37 PST

( from http://www.rxpgnews.com ) Scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have engineered a powerful inhibitor of anthrax toxin that worked well in small-scale animal tests.

"This novel approach to the design of anthrax antitoxin is an important advance, not only for the value it may have in anthrax treatment, but also because this technique could be used to design better therapies for cholera and other diseases," says NIH Director Elias A. Zerhouni, M.D.

The research appears in the April 23 online edition of the journal Nature Biotechnology.

Led by NIAID grantees Ravi S. Kane, Ph.D., of Rensselaer Polytechnic Institute, in Troy, NY, and Jeremy Mogridge, Ph.D., of the University of Toronto, the investigators built a fatty bubble studded with small proteins that can cling tightly to the cell membrane receptor-binding protein used by anthrax toxin to gain entry into a host cell.

The protein-spiked fatty bubble, or "functionalized liposome," hampers a critical early step in the assembly process that anthrax toxin must undergo to become fully active. In test-tube experiments, the inhibitor, which is covered with multiple short proteins (peptides), was 10,000 times more potent than unattached peptides.

"If the effectiveness of anthrax inhibitors designed in this fashion is confirmed by additional testing, they could one day be important adjuncts to standard antibiotic therapy for the treatment of inhalation anthrax," says NIAID Director Anthony S. Fauci, M.D.

The spore-forming bacterium Bacillus anthracis produces a toxin that causes anthrax symptoms. Antibiotics are used to treat anthrax, but even with such therapy, inhalation anthrax, the most severe form of the disease, has a fatality rate of 75 percent.

"There would be real value to having an additional form of therapy available to physicians confronting a case of inhalation anthrax," notes Phillip J. Baker, Ph.D., anthrax program officer at NIAID.

Anthrax toxin has three parts: protective antigen (PA), a protein that binds to a receptor on the target cell surface; and two enzymes that must be transported into the cell to cause damage. The enzymatic portions of the toxin enter the cell through a pore created for them by PA after it binds to the cell's outer surface. PA can be seen as a bundle of seven cigar-shaped parts, a molecular arrangement referred to as "polyvalent," meaning it displays multiple binding sites.

The inhibitor designed by Dr. Kane and his colleagues is also polyvalent. Just as a glove matches the shape of a hand more closely than a mitten, and so fits more snugly, the polyvalent inhibitor binds the toxin at multiple sites and is orders of magnitude more potent than an inhibitor that binds at a single site. The multiple peptides on the functionalized liposome are arranged with the same average spacing as the binding sites of the PA molecule, which permits a firmer bond between the two, explains Dr. Kane. When the inhibitor is bound tightly to PA, the subsequent steps of enzyme entry cannot occur and the toxin is effectively neutralized.

The investigators tested the anthrax inhibitor in rats. When given in relatively small doses, injection of the inhibitor at the same time as anthrax toxin prevented five out of nine rats from becoming ill. Slightly higher doses of the inhibitor prevented eight out of nine rats from being sickened by anthrax toxin. Nine additional rats were injected with anthrax toxin only. Of these, eight became gravely ill. This experiment was the first to show the efficacy of a liposome-based polyvalent inhibitor in animals, says Dr. Kane.

Dr. Kane says the recent experiments demonstrate a proof of principle and suggest that polyvalent inhibitors could be used along with antibiotics in a clinical setting. Aside from its inherent toxicity, anthrax toxin also accelerates the disease process. Thus, combining antibiotics with a toxin inhibitor might act synergistically to lessen or halt anthrax symptoms, notes Dr. Kane.

Using the same technique of placing multiple peptides on a liposome, the researchers also created a polyvalent inhibitor of cholera toxin that functioned well in test-tube experiments.

In the next phase of their research, Drs. Kane and Mogridge and their colleagues plan to test the action of their inhibitor in animals after infecting them with B. anthracis and allowing the disease process to begin. They also will evaluate the inhibitor with and without adjunct antibiotic therapy.

PlyPH protein kills anthrax bacteria by exploding their cell walls

Sat, 22 Apr 2006 17:42:37 PST

( from http://www.rxpgnews.com ) Not all biological weapons are created equal. They are separated into categories A through C, category A biological agents being the scariest: They are easy to spread, kill effectively and call for special actions by the pubic health system. One of these worrisome organisms is anthrax, which has already received its fair share of media attention. But work in Vince Fischettis laboratory at Rockefeller University suggests that a newly discovered protein could be used to fight anthrax infections and even decontaminate areas in which anthrax spores have been released.

Anthrax is the most efficient biowarfare agent. Its spores are stable and easy to produce, and once someone inhales them, there is only a 48-hour window when antibiotics can be used, says Fischetti. Weve found a new protein that could both potentially expand that treatment window and be used as a large-scale decontaminant of anthrax spores. Because anthrax spores are resistant to most of the chemicals that emergency workers rely on to sterilize contaminated areas, a solution based on the protein would be a powerful tool for cleaning up after an anthrax attack.

All bacteria, anthrax included, have natural predators called bacteriophage. Just as viruses infect people, bacteriophage infect bacteria, reproduce, and then kill their host cell by bursting out to find their next target. The bacteriophage use special proteins, called lysins, to bore holes in the bacteria, causing them to literally explode. Fischetti and colleagues identified one of these lysins, called PlyG, in 2004, and showed that it could be used to help treat animals and humans infected by anthrax. Now, they have identified a second lysin, which they have named PlyPH, with special properties that make it not only a good therapeutic agent, but also useful for large-scale decontamination of areas like buildings and military equipment.

The new protein has several advantages. Most lysins, including PlyG, are only active in a very specific pH range of six to seven, so that they work very effectively in our bloodstream, but may not useful in many environmental conditions. PlyPH works in an extremely wide pH range, from as low as four to as high as eight, says Fischetti. I dont know of any other lytic enzyme that has such a broad range of activity.

In addition, PlyPH, like PlyG, is highly specific in terms of the types of bacteria it affects. When Fischetti and colleagues added PlyPH to different bacterial species, only the anthrax bacteria were killed. This is a great benefit over antibiotics, which kill many different kinds of bacteria, including many helpful species. Because it is so specific, the chances of anthrax becoming resistant to PlyPH, as it is to many of the antibiotics currently available to treat it, are extremely low.

We have never seen bacterial resistance to a lysin, says Fischetti. PlyPH and PlyG are probably the most specific lysins we, or anyone, has ever identified they only kill anthrax and its very close relatives. This feature, and the wide pH range offered by PlyPH, is why we think it could be used as an environmental decontaminant.

Fischetti hopes to combine PlyPH with a non-toxic aqueous substance developed by a group in California that will germinate any anthrax spores it comes in contact with. As the spores germinate, the PlyPH protein will kill them, usually in a matter of minutes. The combined solution could be used in buildings, on transportation equipment, on clothing, even on skin, providing a safe, easy way to fight the spread of anthrax in the event of a mass release.

Surprising new insights about the acid pH levels required for anthrax toxin

Wed, 07 Sep 2005 08:10:38 PST

( from http://www.rxpgnews.com ) Surprising new insights about the acid pH levels required for anthrax toxin to invade the cells of the body may help accelerate development of medications for the treatment of anthrax, a disease caused by a spore-forming bacterium.

The anthrax toxin is believed to play a critical role in causing disease symptoms, in many cases leading to death even when antibiotics have been administered to stop bacterial growth. Consequently, there is a great deal of interest in better understanding how the toxin functions so that effective inhibitors with known mechanisms of action can be developed.

The findings, published in the online early edition of the Proceedings of the National Academy of Sciences, come from a joint study by scientists at the Salk Institute for Biological Studies and Harvard Medical School.

This research tells us that we need to revise the model of anthrax toxin entry so that more effective drugs can be developed, says the studys principal investigator, John A. T. Young, Ph.D., a professor in the Infectious Disease Laboratory at Salk. In previous research on the mechanisms used by the anthrax toxin to invade cells, Young's group discovered that the toxin targets two different types of receptors known as TEM8 and CMG2, on the cells surface.

In the new study, Young and his colleagues found that toxin entry occurred at near neutral pH conditions when it was bound to the TEM8 receptor, but at strongly acidic conditions when bound to CMG2. The researchers in Youngs lab at Salk revealed the two different pH levels when they created cells that had only TEM8 receptors or CMG2 receptors, but not both. They then used a drug that neutralizes the pH inside cells to test how it affected toxin entry in both cell types.

To their great surprise, the toxin behaved differently in the two cell types. For cells with the TEM8 receptor, a near-neutral pH was sufficient for toxin entry, but the cells with CMG2 required much more acidic conditions. Although the types of receptors found on different cells in the body have not yet been well defined, the investigators went on to show that different cultured cell lines display either of these two behaviors.

Pore formation and translocation of the toxin occurred under strikingly different conditions, Young says. The finding that receptor type dictates different pH thresholds was completely unexpected.

The lack of a uniform pH threshold suggests that the anthrax toxin may take two alternative pathways to reach different regions inside the cell, and that drugs that target a single pathway may be ineffective, says Jonah Rainey, Ph.D., a research associate in Youngs lab and the lead author of the PNAS paper.

Pharmaceutical agents that are designed to block the acid-dependent route of toxin entry may fail to block the neutral pH-dependent pathway, the researchers say.

In addition, the researchers made a finding that could potentially lead to a new approach for blocking toxin entry into a cell. The toxin forms a syringe-like pore through which the active parts of the toxin can enter the cell.

The scientists found that pore formation is associated with release of the receptor from the toxin. "Prior to this work it was thought that the receptor was only partially released during toxin pore formation but our results suggest that that complete receptor release is required, says Rainey

This is a key new finding, because blocking receptor release might disarm the toxin, says Young.

Rainey adds, A pharmaceutical agent that keeps the receptors locked in their original position may render the anthrax toxin harmless.

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. It is most commonly found in such animals as cattle, sheep and goats, but it can also occur in humans as a result of exposure to infected animals or to anthrax spores used as a bioterrorist weapon, as was the case in 2001 when letters containing spores were mailed through the postal system.

Diagnostic method for identifying Bacillus anthracis receives FDA approval

Tue, 30 Aug 2005 20:55:38 PST

( from http://www.rxpgnews.com ) A method for identifying Bacillus anthracis, the causative agent of anthrax, has been cleared for diagnostic use by the U.S. Food and Drug Administration (FDA). The test, known as the Gamma Phage Assay, was modified by scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) to improve its performance and reliability when used with clinical specimens. The original form of the Gamma Phage Assay was first developed by the Centers for Disease Control and Prevention (CDC) in the mid-1950s.

The modified gamma phage method is the first diagnostic test to gain FDA approval for human use within the Laboratory Response Network (LRN). This network, established by the CDC, is charged with maintaining an integrated system of state and local public health, federal, military, and international laboratories that can respond to bioterrorism, chemical terrorism and other public health emergencies.

According to USAMRIID senior scientist John W. Ezzell, the Gamma Phage Assay is a classical bacteriological method that has been used at USAMRIID and other laboratories for years as part of an extensive array of methods used to identify B. anthracis. The gamma phage is a virus capable of entering bacterial cells and causing cell destruction, or lysis--and it is specific to B. anthracis.

"Because of that specificity, the gamma phage gives a highly readable result," Ezzell explained. "Wherever the virus is added to the surface of a culture plate that has been inoculated with suspicious anthrax colony growth, you can see clear zones where the B. anthracis cells have been destroyed--whereas other bacterial cells grow unaffected."

Well before the anthrax attacks of 2001, scientists at USAMRIID and the CDC recognized the need for an FDA accepted method for identifying B. anthracis in clinical specimens. In 2002, FDA's Division of Clinical Laboratory Devices agreed to recognize tests for B. anthracis as eligible for classification with a 510(k) premarket notification process--the designation given to devices and other non-biologics.

USAMRIID, with support from CDC, prepared and submitted a 510(k) Premarket Notification using both USAMRIID and CDC data on use of the gamma phage method. With FDA recognition of the assay as substantially equivalent to the classical assay used prior to 1976, it will be available for use for testing in designated civilian and military clinical laboratories.

"This is a big first step in helping to provide the LRN labs with FDA cleared assays," said Judy Sheldon, a regulatory affairs microbiologist with the CDC's Bioterrorism Preparedness and Response Program. "The work done at USAMRIID and here at CDC provided a solid scientific basis for FDA to evaluate the assay performance. This work has set a high bar for other tests to meet."

USAMRIID scientists standardized and validated the test to make it more rugged, more reproducible across laboratories, and more resistant to user error. They developed a clearly defined method for production of gamma phage that proved to be highly stable, as reflected in the extended shelf life of the B. anthracis-specific virus. USAMRIID then provided sufficient gamma phage material to CDC for distribution within the LRN, so that each laboratory will have the same material to be used in the test. In addition, USAMRIID developed Standard Operating Procedures for the assay to ensure that each laboratory in the LRN will run the test the same way. This also increases confidence in the final result.

"This represents a very significant milestone for both of our organizations, in that all of the medical diagnostic products that we are developing must eventually follow a similar pathway for approval to allow clinical diagnosticians to use these tests to positively identify pathogens," said Colonel George W. Korch, Jr., commander of USAMRIID. "Successes such as these demonstrate that we can translate our research efforts into products for our health care providers and clinical laboratory professionals."

Protective Antigen Ion Channel Asymmetric Blockade To Detect Anthrax Infection

Mon, 29 Aug 2005 22:03:38 PST

( from http://www.rxpgnews.com ) A new laboratory method for quickly detecting active anthrax proteins within an infected blood sample at extremely low levels has been developed by researchers at the National Institute of Standards and Technology (NIST), the U.S. Army Medical Research Institute of Infectious Diseases and the National Cancer Institute.

Current detection methods rely on injecting live animals or cell cultures with samples for analysis and require up to several days before results are available. Described* in an upcoming issue of the Journal of Biological Chemistry, the new method produces unambiguous results in about an hour. The researchers hope the system will ultimately be useful in developing fast, reliable ways to diagnose anthrax infections or to quickly screen large numbers of drugs as possible therapies for blocking the bacteria's toxic effects.

The method works by detecting changes in current flow when anthrax proteins are present in a solution. An anthrax protein ironically called "protective antigen" spontaneously forms nanometer-scale pores that penetrate the surface of an organic membrane. When a voltage is applied across the membrane, positively and negatively charged ions flow freely in both directions through the pore. When additional anthrax proteins called lethal factor (LF) or edema factor (EF) are present, however, the proteins bind to the outside of the pore and shut down the flow of ions in one direction. This change in current flow depends on the concentration of the proteins in the solution and can detect amounts as low as 10 picomolar (trillionths of a mole).

"We hope this system will lead to a method for rapidly screening agents that inhibit the binding of LF or EF to these pores," says NIST's lead investigator John Kasianowicz.

A computer model shows side and top views of two different proteins produced by anthrax bacteria. The green molecule is "protective antigen" (PA), which spontaneously forms pores that penetrate organic membranes such as cell walls. The yellow molecule is "lethal factor (LF)." When a voltage is applied across a membrane studded with PA pores, both positive and negative ions flow through. Once LF binds to the pore, however, current only flows in one direction. Image credit: T. Nguyen, National Cancer Institute

Live anthrax antibodies seem to do exactly that. When antibodies were present in the test solution and then LF was added, the current flow remained unchanged, indicating that the anthrax proteins were unable to bind properly. The long-term goal would be to find drugs with few side effects that also interfere with this binding process.

ABthrax(TM) Safe and Effective against Anthrax

Mon, 25 Jul 2005 11:12:38 PST

( from http://www.rxpgnews.com ) Human Genome Sciences, Inc. (HGSI) announced today that results published in the current issue of Clinical Infectious Diseases demonstrate that the first investigational agent against anthrax infection to be evaluated in a clinical study since the 2001 anthrax attacks in the United States, is safe, well tolerated and achieves the blood levels predicted by relevant animal models as necessary to afford significant protection from the lethal effects of the anthrax toxin.(1, 2)

ABthrax(TM), a fully human monoclonal antibody to Bacillus anthracis protective antigen, was studied in a randomized, single-blind, placebo- controlled, dose-escalation Phase 1 clinical trial in 105 healthy adult volunteers. The trial was designed to evaluate the safety, pharmacokinetics and biological activity of ABthrax.(3)

The subjects received a single intramuscular injection (11 subjects/cohort) or intravenous infusion (10 subjects/cohort) of either ABthrax or placebo. Three intramuscular (0.3, 1.0 and 3.0 mg/kg) and five intravenous (1.0, 3.0, 10.0, 20.0 and 40.0 mg/kg) dose levels were studied. Two separate intramuscular injection sites (gluteus maximus and vastus lateralis) were evaluated. The primary endpoints of the Phase 1 trial were safety and tolerability. Pharmacokinetics, immunogenicity and parameters of biological activity also were evaluated.

Results show that ABthrax was safe, well tolerated and bioavailable after a single intramuscular or intravenous dose, with no dose-limiting adverse events. Only transient, mild-to-moderate adverse events were observed, with no statistically significant difference in adverse event profiles between active and placebo arms of the study. Pharmacokinetic analysis demonstrated that the half-life of ABthrax ranged from 15 to 19 days. The biological activity of ABthrax correlated with serum concentrations. In the Phase 1 study, ABthrax concentrations were achieved that are comparable to, or in excess of, anti-protective antigen antibody levels that correlated with significant protection in relevant animal models of inhalational anthrax.

Mani Subramanian, M.D., lead author and Director of Clinical Research, Infectious Diseases, said, "This report describes the first investigational agent against inhalational anthrax infection to be evaluated in a clinical study since the 2001 anthrax attacks in the United States. We have shown that ABthrax can be safely administered, is well tolerated, and is able to achieve levels of concentration in the blood that are comparable to levels that correlated with significant protection in relevant animal models of inhalational anthrax. Preclinical studies in relevant animal models have demonstrated the dose-related efficacy of ABthrax in both prevention and treatment of anthrax disease.(4-10) The results of one such study showed that nonhuman primates that survived anthrax spore exposure following a single dose of ABthrax produced a robust immune response against the anthrax toxin that persisted at six months and nearly a year later.(6) Based on the results of the Phase 1 study, as well as the strongly supportive results of studies in relevant animal models of inhalational anthrax, we believe that further expanded safety studies with a larger number of subjects are warranted, as well as additional combination studies of ABthrax with antibiotic and vaccine agents."

James H. Davis, Ph.D., J.D., Executive Vice President and General Counsel, said, "We have advanced ABthrax to this point using our company's own resources and at our own risk, without receiving any financial assistance from the government. Guidelines were set forth in the Bioterrorism Act of 2002(11) for the development of treatments for disease organisms such as anthrax, which have high potential for use in bioterrorist attacks. The Bioterrorism Act recognizes that there is no practical way to conduct a clinical trial of the efficacy of a drug designed to treat a disease such as anthrax, which only rarely occurs in humans. The Bioterrorism Act states that successful studies in relevant animal models will be considered sufficient to establish efficacy for licensure and marketing approval, and states that a clinical trial in humans will be required to establish safety. In accordance with the Bioterrorism Act and consistent with current FDA guidance, we have shown in animals that ABthrax is effective against high doses of inhalation anthrax, and we have demonstrated initial safety in humans. In addition, we have developed the required assays and a scalable purification process that will enable Human Genome Sciences to manufacture the drug.(12)

"We have been ready to begin manufacturing of this product and to initiate additional human safety trials for over a year and a half, but the cost of the next phase of development is much too high for any biopharmaceutical company to undertake on a speculative basis. To move forward with further development of ABthrax, we need to bring to a favorable conclusion the lengthy procurement process now underway, and for the federal government to enter into a contract under the Project Bioshield Act of 2004 for the purchase of the drug for the Strategic National Stockpile. Once a contract is signed, and depending on the government's requirements, this key biodefense countermeasure could be available for emergency use in approximately one year from the date of a firm order."

The Need for New Means to Fight Anthrax Infections

Currently, two options are available for the prevention or treatment of anthrax infections -- a vaccine and antibiotics. Both are essential to dealing with anthrax, but both have limitations. The anthrax vaccine takes several weeks following the first doses before immunity is detectable. The vaccine also requires multiple injections over a period of eighteen months, in addition to annual boosters, to maintain its protective effect. Antibiotics are effective in killing anthrax bacteria, but are not effective against the anthrax toxins once those toxins have been released into the blood. Antibiotics do not provide the opportunity for development of protective immunity to future exposures. Antibiotics also may not be effective against antibiotic-resistant strains of anthrax.

In ABthrax, Human Genome Sciences discovered and developed a third mechanism of defense against anthrax infections. In contrast to the anthrax vaccine, the protection afforded by a single dose of ABthrax would be immediate following the rapid achievement of appropriate blood levels of the antibody. In contrast to antibiotics, ABthrax acts against the lethal toxins produced by anthrax bacteria. It may also prevent and treat infections by antibiotic-resistant strains of anthrax.

ABthrax is a human monoclonal antibody to Bacillus anthracis protective antigen that was discovered and developed by Human Genome Sciences. ABthrax was developed using technology that Human Genome Sciences has integrated into the Company as part of its collaboration with Cambridge Antibody Technology.(13) In 2003, ABthrax received a Fast Track Product designation from the FDA.(14)

Anthrax infection is caused by a spore-forming bacterium, Bacillus anthracis, which multiplies in the body and produces lethal toxins. Most anthrax fatalities are caused by the irreversible effects of the anthrax toxins.(15) Research has shown that protective antigen is the key facilitator in the progression of anthrax infection at the cellular level.(15-17) After protective antigen and the anthrax toxins are produced by the bacteria, protective antigen binds to the anthrax toxin receptor on cell surfaces and forms a protein-receptor complex that makes it possible for the anthrax toxins to enter the cells. ABthrax blocks the binding of protective antigen to cell surfaces and prevents the anthrax toxins from entering and killing the cells.

DNI - Newly Identified Inhibitor of Anthrax Toxin May Contribute to Postexposure Therapy

Mon, 20 Jun 2005 16:07:38 PST

( from http://www.rxpgnews.com ) A newly identified inhibitor of the anthrax toxin may be used to develop a safer and more effective vaccine and act as a therapeutic agent after exposure say researchers from Massachusetts and Germany. Their findings appear in the June 2005 issue of the journal Infection and Immunity.

Anthrax is a highly contagious and toxic disease that results from infection with the bacterium Bacillus anthracis. If not caught immediately, those infected may die within a matter of days. Anthrax poses a deadly threat as a potential biological weapon placing added emphasis on the need for a safe and effective vaccine. The vaccine currently available doesn't protect against the bacilli and may be hazardous to its host when used immediately after exposure.

In the study researchers infected two groups of mice with anthrax and immunized one group with a dominant-negative inhibitor (DNI) and the other with a protective antigen (PA) currently used in the anthrax vaccine. They monitored the mice for several weeks and found that DNI alone produced higher immune responses than PA. Due to DNI's ability to inhibit the anthrax toxin, researchers also believe that DNI-based vaccines may increase immunity and provide therapeutic activity when administered postexposure.

"The strong immunogenicity and retained antigenicity of DNI suggest that DNI is a promising and potentially safer candidate for use in an anthrax vaccine than PA," say the researchers. "Moreover, in the event of anthrax infection, the administration of DNI can serve not only as an antitoxic therapy as an immediate response but also as a prophylactic vaccine to prevent late-onset or future anthrax infection."