JSTOin the News

DTRA.mil

April 2016 | Vol. 6 No. 4

Approved for public release, distribution is unlimited

Chemical Agent Trajectory Patterns

Fighting Ebola with Human Antibodies

Blueprinting the Way to Warfighter Safety

Lead DoD science and

technology to anticipate,

defend and safeguard

against chemical and

biological threats for the

warfighter and the nation.

DEFENSE THREAT REDUCTION AGENCY & USSTRATCOM Center for Combating WMD & Standing Joint Force Headquarters-Elimination

J9 Research and Development Directorate Chemical and Biological Technologies

8725 John J Kingman Road, Stop 6201, Fort Belvoir, VA 22060

www.dtra.mil

Handle: @cbdstconference

Keyword: DTRA

Channel: doddtra

On the front and back covers: Marines and Sailors of the Chemical Biological Incident Response Force (CBIRF) conduct a live chemical agent exercise at Fort A.P. Hill, Virginia, on April 10, 2014. The unit conducted simulated casualty extraction in clouds of CS gas to prepare for real life evacuation situations. In order to execute its mission, CBIRF possesses a wide variety of unique skill sets that address all possible aspects of a CBRNE attack. CBIRF has six major sections organic to the battalion: Explosive Ordnance Disposal, Technical Search and Rescue, Decontamination, Medical, Identification and Detection, and Search and Rescue/Casualty Extraction. (Official Marine Corps Photo by Sgt Kuande L. Hall)

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SME @ email address 3

Exposure to a chemical or biological agent poses serious risks to warfighters. Accurately modelling the trajectory patterns of chemical and biological warfare agents is critical to ensure the safety of our combat forces.

Projects by the Defense Threat Reduction Agency’s Joint Science and Technology Office are increasing warfighter safety by enhancing modeling capabilities of deadly chemical and biological agents. Understanding factors that influence the behavior of toxic chemicals and pathogens will influence the development of new countermeasures that could protect the warfighter and enable mission completion in environments compromised by these agents.

Existing knowledge regarding the molecular interaction between chemical and biological agents and the atmosphere or environmental surfaces is limited and presents a significant challenge to current modeling capabilities.

Quantitative structure-activity relationship (QSAR) models are only applicable to some volatile organic compounds. Those same models also lack highly sensitive qualitative and quantitative methods to characterize reactivity and predict efficacy and hazards when reaction rates are unknown. However, efforts within JSTO’s Basic Research Environmental Availability Program are leveraging innovative technologies and methodologies to reveal new information about the ways molecules interact and react in complex environments. Recently a basic research project, managed by Dr. Brian Pate of JSTO and published in The Journal of Physical Chemistry A article, “Scattering Dynamics, Survival, and Dispersal of Dimethyl Methylphosphonate Interacting with the Surface of Multilayer Graphene,” highlighted the promising results.

Utilizing state-of-the-art gas surface interaction instrumentation and methods to characterize molecular exchanges with substrates, researchers demonstrated the efficacy of using kinetic energy controlled molecular beams to investigate the interactions of dimethyl methylphosphonate (DMMP), a nontoxic sarin simulant. DMMP has a well-defined surface (graphene) which improved the research team’s understanding of scattering dynamics. This breakthrough demonstrates the need to accurately model multiple bounce trajectories of the impinging molecules during the dispersal of chemical warfare agents in the environment.

In addition, Dr. Tony Esposito, Mike Roberts, Dale Taylor and Rick Fry are leading other environmentally focused JSTO efforts. These complementary projects include the prediction of physico-chemical properties using empirical QSAR methods and theoretical ab initio methods.

Useful molecular descriptors are needed to quantitatively predict specific reaction rate constants. A new collaborative effort between JSTO and the U.S. Army Edgewood Chemical and Biological Center is exploring environmental effects for chemical warfare simulants on relevant operational surfaces.Developing highly sensitive qualitative and quantitative experimental methods that probe sticking coefficients and subsurface concentration gradients of contaminants will lead to the identification of new transport mechanisms. This knowledge will enhance modeling tools that enable the prediction of technology efficacy and hazards for a range of known agents, materials, decontaminants and environmental conditions. It will also provide the capability to approximate the degradation chemistry for yet-to-be-characterized chemicals, leading to better protections for the warfighter.

Modeling New Trajectory Patterns of Chemical Agents

POC: Dr. Brian Pate; brian.d.pate.civ@mail.mil

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DMMP interacting with a graphene surface. Image courtesy of The Journal of Physical Chemistry A.

SME @ email address4

LETHAL WEAPON

Fighting Ebola with

Human Antibodies

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There have been 24 Ebola outbreaks since 1976 though none as deadly as the recent West African epidemic. New research conducted by the Defense Threat Reduction Agency’s Joint Science and Technology Office, uses neutralizing antibodies to reduce mortality rates in Ebola infected animals. This research could inspire medical countermeasures to better protect warfighters, civilians and humanitarian aid workers against future outbreaks.

The Ebola virus can infect humans and primates, causing a hemorrhagic fever with mortality rates up to 90 percent. The recent outbreak, from December 2013 to January 2016, resulted in more than 28,000 cases and 11,000 deaths. Although Ebola poses a high public health threat, no licensed treatment or vaccine for filovirus infection currently exists. Recently, several studies showed that filovirus glycoprotein (GP)-specific neutralizing antibodies can reduce mortality following experimental inoculation of animals with a lethal dose of the Ebola virus.

A basic research project managed by JSTO’s Dr. Ilya Elashvili, and performed in conjunction with Vanderbilt University and the University of Texas Medical Branch at Galveston, isolated a large panel of fully human monoclonal antibodies to Ebola. This research demonstrated efficacy in treatment of experimentally infected animals and clarified the mechanism of filovirus inhibition. The results of this effort have been recently reported in a comprehensive study in the Cell article, “Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.”

The article described how the research team, led by Dr. James Crowe, isolated a panel of antibodies that bind to Ebola virus GP from human survivors. Subsequent studies identified antigenic sites where these antibodies interact. They found that the neutralizing antibodies recognize diverse major antigenic sites on GP.

Single-particle electron microscopy structures of antibody-GP complexes revealed that the neutralizing antibodies bind to Ebola virus GP at regions called the glycan cap, or to a site lower down on the GP in the stem region of the protein.

The researchers found that the epitopes where many of antibodies interact is highly conserved in a range of Ebola virus-species, including Ebola Zaire, Bundibugyo and Sudan. The data obtained through these studies elucidates the mechanism of the virus’ neutralization, as they indicate the human Ebola virus-neutralizing antibodies bind to infectious viruses at the glycan cap and inhibit structural rearrangements necessary for attachment and entry.

The human antibodies were found to be effective to treat otherwise lethal experimental Ebola infection in mice and guinea pigs. This new knowledge could help develop broad-spectrum protective remedies, such as broadly neutralizing antibody and universal structure-based vaccine designs, and detection capabilities against the existing filoviruses and emerging viral strains.

Dr. Crowe’s laboratory is collaborating with academic and industrial partners that are conducting preclinical studies on Ebola antibodies, which could protect warfighters and humanitarian aid workers responding to outbreaks as well as the local at-risk population.

Studies funded by JSTO suggested that antibody-mediated protection against multiple strands of the Ebola virus may be achievable. Dr. Crowe and his team isolated a large panel of human monoclonal antibodies against the glycoprotein using peripheral blood B cells from survivors of the 2007 Ebola outbreak in Uganda. The cells provided potent neutralizing activity. These results provide a promising roadmap to developing a single antibody-based treatment effective against multiple Ebola strands. Image courtesy of Cell.

POC: Dr. Ilya Elashvili; ilya.elashvili.civ@mail.mil

POC: Michael Roberts; michael.a.roberts212.civ@mail.mil 55

Blueprints are critical for success when building infrastructure, whether constructing a skyscraper or software system. Creating a blueprint of how to better protect warfighters led the Defense Threat Reduction Agency to fund a software tool that can quickly model how harmful agents affect warfighter shelters and equipment during a chemical or biological attack.

Led by Mr. Michael Roberts from DTRA’s Joint Science and Technology Office, the Department of Defense’s Joint Expeditionary Collective Protection (JECP) program recently accredited JSTO’s System Performance Model (SPM) as a simulator that can model how harmful agents affect warfighter shelters and equipment during a chemical or biological attack. The SPM simulates trial conditions with a uniform exterior contaminant concentration, increasing warfighter safety by reducing the time and money previously needed for physical tests.

Shelter systems utilize collective protection concepts such as air filtration, over pressure, highly resistant barrier materials, and airlocks to defend the toxic free area of the shelters. Personnel exposed to a chemical or biological agent; however, will become contaminated from the released chemical or biological agent as some

portion of the agent will adhere to their clothing. The amount of agent adherence is dependent on concentration levels and duration of exposure.

Prior to JSTO’s SPM software, JECPs were lacking a dynamic software that could model how chemical and biological agents influence the infrastructure’s ability to protect the warfighter from contaminants.

Principle investigator Harold Barnette from the Naval Surface Warfare Center, developed the SPM predictive modeling software application to address risks associated with personnel movement and off-gassing. Through supplementing laboratory, chamber and field test data with simulation results, the SPM software will improve JECP System shelters to protect the warfighters inside and minimize contamination for those seeking protection.

Similar to a blueprint, the SPM models the dynamic components of JECP Systems by using single or complex configurations. Users pair the appropriate contaminant with environmental conditions, such as shelter configurations and terrain to model the off-gassing.

Within the shelter configuration, the SPM models specific features of JECP shelters

designed to protect against chemical and biological agents. For example, the SPM can represent the behavior of the fan filter assembly, including the performance of the M98 HEPA and carbon filters. It also models the regulation of shelter overpressure facilitated by the JECP Dial-a-Flow orifices. Without shelter filters and overpressure, contaminants could enter into the shelter, making them important components in accurately simulating the shelter performance against agent threats.

Additionally, the SPM simulates the effects of contaminant leakage from the external environment through the environmental control unit. Adding the impact of personnel to the simulation, the model can simulate the transport of contaminated air into the toxic free area and personnel entrance that occurs during personnel movement (ingress and egress events). The software also incorporates the absorption and desorption of contaminant vapor on personnel clothing and from the interior of the shelter itself.

As the modeling and simulation development progresses, this accreditation approval milestone will supplement laboratory, chamber and field test data. Utilizing the SPM model, engineers can develop better shelters, equipment, and procedures to keep warfighters safe from chemical and biological threats.

BLUEPRINTING THE WAY TO WARFIGHTER SAFETY

Within the Defense Threat

Reduction Agency’s Research

and Development Directorate,

resides the Joint Science and

Technology Office for Chemical

and Biological Defense. This

publication highlights the

organization’s accomplishments

to protect warfighters and

citizens through the innovative

application of science and

technology research.

DTRA

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