VeloThrax™ – Anthrax Vaccine pre and post-exposure
VeloThrax™ is Soligenix's newly acquired proprietary vaccine based on a recombinant Protective Antigen (rPA) derivative intended for use against anthrax. Soligenix has entered into an exclusive license option with Harvard College to license VeloThrax™ (also known as DNI for dominant negative inhibitor). VeloThrax™ is a translocation-deficient mutant of PA with double mutations of K397D and D425K that impede the conformational changes necessary for endosomal membrane translocation into the cell cytoplasm. In the absence of that PA translocation step, anthrax toxin trafficking and function cease. VeloThrax™ is also considered a more immunogenic candidate than native rPA. This apparent increase in immunogenicity suggests that the DNI rPA is processed and presented to the immune system more efficiently by cellular antigen processing pathways, which is consistent with known properties of the molecule.
Initial development work on VeloThrax™ has begun and will be conducted pursuant to Soligenix's $9.4 million National Institute of Allergy and Infectious Diseases (NIAID) grant enabling development of thermo-stable ricin and anthrax vaccines. VeloThrax™'s greater immunogenicity could lead to a vaccine that can be administered in the fewest possible doses to induce the highest level of toxin neutralizing antibodies. Utilizing ThermoVax™, Soligenix believes that it will be able to develop VeloThrax™ into a vaccine with an improved stability profile, an issue that has proven challenging in the development of other anthrax vaccines. Extended stability at ambient temperatures would be a significant improvement for stockpiled vaccines and one which is not expected from conventional vaccines. Further, a large-scale, current Good Manufacturing Practice (cGMP) production methodology has already been completed. Assuming long-term stability can be met, VeloThrax™ could be stockpiled for general prophylactic as well as a post exposure use.
The overall objective of the VeloThrax™ program is to rapidly and efficiently develop a next generation anthrax vaccine which combines a well established, safe and relatively low risk vaccine development and dosing approach with targeted, proven innovative strategies. VeloThrax™ will potentially be a combination of a stable, readily manufactured mutant rPA subunit antigen with next generation, clinically compatible adjuvants which have been demonstrated to enhance potency and reduce the time and number of vaccine doses required to achieve protective titer using a variety of vaccine antigens. This blend of proven yet innovative technologies will provide the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) and the Department of Defense (DoD) with a safe and stable alternative to the existing licensed anthrax vaccine product. Soligenix also proposes to adapt newly developed glassification technology (initially developed under an ongoing NIAID grant to stabilize exceptionally unstable ricin toxin/adjuvant formulations) to enable a thermostable, dried, single vial, pre-formulated adjuvanted rPA vaccine which is suitable for both long term storage and field use without typical cold chain constraints.
Anthrax as a biological weapon
Anthrax or Bacillus anthracis has long been regarded as the number one bio-terror threat by the Department of Homeland Security due to its ability to be easily weaponized and distributed over large metropolitan areas by planes and through ventilation systems. As a consequence, this pathogen is designated as a Category A biothreat by the CDC.
As defined by the CDC, anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Anthrax most commonly occurs in hoofed mammals, and can also infect humans. Symptoms of disease vary depending on how the disease is contracted, but usually occur within seven days after exposure. The most serious forms of human anthrax disease are inhalational anthrax, cutaneous anthrax, and gastrointestinal anthrax. Initial symptoms of inhalational anthrax infection may resemble a common cold. After several days, the symptoms may progress to severe breathing problems and shock. Inhalational anthrax is often fatal, even if treated by antibiotics. Currently, antibiotics are the only drugs available for therapeutic or prophylactic use for inhalational anthrax, and post-exposure prophylaxis is the only anthrax-related FDA-approved indication for such products. However, antibiotic therapy, while useful, is believed to be associated with a number of limitations, including: (1) lack of activity against the toxins produced by the B. anthracis bacteria, (2) need for long-term dosing to achieve full protection, complicated by side effects and non-compliance, (3) lack of efficacy when administered late in the anthrax disease cycle, and (4) lack of effectiveness against multi-drug resistant or genetically engineered strains of anthrax.
Beginning in the second half of the 20th Century, anthrax was developed by several countries (including the Soviet Union and the US) as part of their biological weapons (BW) programs. Since that time, the US, Russia, and many other countries have discontinued offensive BW programs. However, some programs still may be in operation.
After the Second World War, the US continued its biological weapon research into the 1950s, when Iowa State University produced the virulent "Ames strain" of anthrax which was later sold in many parts of the world. In 1970, President Nixon ordered an end to the production of biological weapons in the US. By 1972, international concern led to a treaty banning the production and stockpiling of biological weapons, which was eventually signed by some 140 nations. Although it was one of the treaty signatories, the Soviet Union continued researching and producing biological weapons - and in April 1979 an accidental release of anthrax spores from a military facility near Sverdlovsk caused 68 known deaths.
Autonomous groups have also demonstrated an intent to use anthrax in acts of terrorism. For example, as evidenced in a March 10, 2007, Department of Defense transcript of the Tribunal Hearing of Khalid Sheikh Muhammad, Al Qaeda leadership has shown interest in and has worked to develop anthrax and other biological weapons. Most notably, in October 2001, anthrax attacks were perpetrated in the US via the mail, when at least 5 envelopes containing B. anthracis spores were sent through the US postal system (four were recovered). All of the letters were presumed to have been mailed from Trenton, New Jersey. Twenty-two cases of anthrax resulted (11 inhalational, 11 cutaneous), and 5 people died from inhalational anthrax.
A 1970 analysis by the World Health Organization (WHO), updated in 2004, concluded that the release of aerosolized anthrax upwind of a population of 5,000,000 could lead to an estimated 250,000 casualties, of whom as many as 100,000 could be expected to die. Following the 2001 anthrax attacks, the US government recognized the need to develop more effective therapeutic countermeasures to protect Americans from a large-scale attack. Importantly, anthrax has been designated a significant material threat by the Department of Homeland Security prompting the need to stockpile more effective countermeasures. Further, the potential use of anthrax toxin as a biological weapon of mass destruction has been highlighted in an FBI Bioterror report released in November 2007, entitled Terrorism 2002-2005, which states that "Ricin and the bacterial agent anthrax are emerging as the most prevalent agents involved in Weapons of Mass Destruction (WMD) investigations".
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