Antibodies may provide new anthrax options

Avanir Pharmaceuticals, from San Diego, CA, has presented positive new data on its panel of human antibodies against anthrax.

Two of its most potent anthrax antibodies, AVP 21D9 and AVP 22G12, appear unique both in mechanism of action and in terms of the binding site on the anthrax toxin.

AVP 21D9 and AVP 22G12 completely inhibit toxin complex assembly, and do so by attaching to distinct domains of the toxin. The antibodies bind to the anthrax toxin with a very high affinity, in the picomolar range. Additionally, these are two of Avanir's most potent anthrax toxin neutralising antibodies, exhibiting neutralising potency in the stoichiometric range. Also notable in terms of potency, a third antibody, AVP 1C6, inhibits the anthrax toxins through a mechanism that involves the blockade of host cell receptor recognition, a more commonly used approach.

'AVP 21D9 and AVP 22G12 disrupt the assembly of the anthrax toxin, rendering it incapable of entering cells,' noted Dr Angray Kang, Avanir's associate director of antibody technology. 'To our knowledge, no other companies working in this area have demonstrated that their antibodies neutralise anthrax toxins by targeting this step. In addition to antibodies with this unique mechanism, we also have antibodies that are very potent but have mechanisms of action similar to the approach being developed by other companies. We feel this wide array of choices is advantageous and is due to the prolific nature of our Xenerex antibody technology.'

About AVP 21D9

AVP 21D9 is one of a panel of human monoclonal antibodies discovered and developed by Avanir Pharmaceuticals using its Xenerex technology. Preclinical research to date demonstrates that a single dose of AVP 21D9 completely protects rats subsequently challenged with a lethal dose of recombinant anthrax toxins one week later. AVP 21D9 is a potent inhibitor of protective antigen (PA) transition to the PA multimer. Anthrax fatalities are caused by the irreversible effects of the toxins produced by the spore-forming bacteria, Bacillus anthracis, once it enters the body. Protective antigen is a component of the anthrax toxins that plays a pivotal role in providing a portal for lethal factor (LF) and edema factor (EF) to enter into the intracellular compartment and exert a lethal effect. By neutralising PA, AVP 21D9 effectively prevents the anthrax LF and EF toxins from entering the cells. With AVP 21D9, AVANIR has bridged the gap between antibiotic use and conventional vaccination. In contrast to the anthrax vaccine, the protection afforded by a single dose of AVP 21D9 would be immediate. In contrast to antibiotics, AVP 21D9 acts against the key gateway component, PA, of the anthrax toxin. Although speculative, AVP 21D9 may also play a role in the prevention and treatment of infections by antibiotic-resistant strains of anthrax. Therefore, it could potentially be utilised in multiple scenarios, augmenting vaccination and/or antibiotic therapy or in a stand-alone prophylaxis or therapeutic modality.

Current anthrax antidotes

Currently, two options are available for the prevention or treatment of anthrax exposure, a vaccine and antibiotics. Both approaches have limitations. The current anthrax vaccine may take several weeks following the first doses before immunity is established, and requires multiple injections over a period of eighteen months, in addition to an annual booster injection, to maintain its putative protective effect. This may be adequate for "preparedness" in the armed forces, or for first line responders, but is of limited use to the civilian population. Alternatively, antibiotics, the standard treatment of anthrax infection, are effective in killing anthrax bacteria, but are usually only effective when given immediately after exposure or upon suspicion of exposure to anthrax. Antibiotics are of limited use once the anthrax toxins are released. Moreover the natural emergence or deliberate release of antibiotic-resistant strains of anthrax is an ongoing concern.