ADAMANT about Warfighter Protection

Courtesy Photo | Spc. Keegan Carlson, a civil affairs specialist with the 440th Civil Affairs Battalion in Colorado Springs, Colo., pulls an improvised litter during the reacting to a chemical environment evaluation as part of the Department of the Army Best Warrior Competition here in Fort Lee, Va. Carlson is the U.S. Army Reserve Command Soldier of the Year and is one of 14 Soldiers competing for the DA Soldier of the Year category.  

FORT BELVOIR, VA, UNITED STATES

09.19.2019

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Exposure to biological warfare agents, such as the botulinum neurotoxin, can be fatal. The neurotoxin is naturally released by the bacterium Clostridium botulinum that lives in soil, but it can also be manufactured in large quantities. A single gram of it — inhaled or ingested — could kill over a million people.

Because botulinum poisoning resembles other conditions (stroke or an opioid overdose), correct diagnosis can take time. Treatment is an antitoxin, but recovering from any muscle or neurological injury a warfighter sustained before diagnosis could require a hospital stay of weeks to months.

Advances in medicine are needed, not only to speed up the recovery time but also to take as prophylaxis (medicine) before an exposure occurs to prevent any harm. The U.S. Executive Branch’s 2018 National Biodefense Strategy calls for the development of platform and innovative technologies that accelerate the development, production, and availability of medical countermeasures to mitigate the impact of such poisoning.

To accelerate this medical research, the Defense Threat Reduction Agency’s Chemical and Biological Technologies Department (DTRA CB) is developing the ADAMANT platform — the Advanced Development and Manufacturing of Antibody Technologies — at the DoD’s Advanced Development and Manufacturing facility in Florida.

The ADAMANT platform uses human-derived proteins, called humanized antibodies, to develop medicines that fight pathogens and toxins. The first medicine currently being developed in ADAMANT binds to and neutralizes botulinum neurotoxin serotypes A and B, which are among the world’s most poisonous toxins. In a matter of hours, exposure to either A or B causes paralysis, respiratory failure, or death. To develop and manufacture medicines in ADAMANT, DTRA CB is working with the Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense’s Joint Project Management Office for Medical Countermeasure Systems.

The humanized antibodies that ADAMANT uses are monoclonal, which are single proteins and ones that always bind to a specific part of a pathogen or toxin. Monoclonal antibodies (mAbs) are able to identify a specific antigen (i.e., bacteria, viruses, and other foreign bodies), or region on a pathogen or toxin. This identifying characteristic makes mAbs a highly specific drug to neutralize the given pathogen or toxin.

The Food and Drug Administration (FDA) has approved nearly 80 mAb products. If ADAMANT can successfully create a medical product consisting of multiple mAbs to combat botulinum serotypes A and B, then researchers will proceed to the validation step, which is to test the ADAMANT platform with an mAb-based product that targets a second pathogen. A successful validation would mean that the platform performs as designed, firmly establishing ADAMANT’s ability to create mAbs for use in medicines that counter toxins and other pathogens, thereby better protecting warfighters and the nation.

Drugs based on mAbs have a rapid onset of protection, but this effect lasts only a few weeks to months. While mAb-based medicines cannot replace the long-term protection (months to years) a vaccine would offer, they do provide rapid protection from a biological agent on short notice and in conflict settings where toxins or other biological agents are deployed. This rapid protection is paramount because vaccines do not yet exist for every toxin or pathogen.

If successful, ADAMANT promises an mAb-based drug to protect against botulinum neurotoxin types A and B. Warfighters could receive the medicine as an injection in the muscle (intramuscular), rather than in the vein, which meets the DoD’s logistical requirements. Furthermore, the final drug product will be available in a freeze-dried formula to extend its shelf life and enhance its environmental stability.

The botulinum mAb product has passed several developmental milestones, and the FDA will receive an Investigational New Drug application for the product sometime in 2019. Clinical safety trials in healthy human volunteers will begin in 2020. Several nonclinical animal studies have demonstrated 100% protection against high doses of aerosolized botulinum toxin when the mAb antitoxin is delivered intramuscularly. FDA approval is predicted for 2025, which is significantly faster than traditional medical product development.

Successful field-testing of the mAb product for botulinum neurotoxin serotypes A and B will go far in demonstrating ADAMANT as a superior manufacturing platform. Establishing and validating a process to discover, design, manufacture, and test new humanized mAbs will greatly accelerate the development of subsequent mAb-based medical products to protect our warfighters.


POC: Traci Pals, Ph.D., [e-mail]

• Date Taken: 09.19.2019
• Date Posted: 09.25.2019 17:25
• Story ID: 343748
• Location: FORT BELVOIR, VA, US