TOPIC CALL 1.pdf

Approved For Public Release

THE PHASE 1 PROPOSAL SUBMISSION DEADLINE FOR THE

FOLLOWING TOPICS IS AUGUST 16, 2022 AT 2:00PM EASTERN

DAYLIGHT TIME (EDT).

THE DEADLINE TO SUBMIT QUESTIONS RELATED TO THE

FOLLOWING TOPICS IS JUNE 29, 2022.

CBA-01

Novel Sampling and Diagnostics Methods for the Warfighter

Background: Warfighters are often deployed to austere environments under potential chemical and biological warfare agents (CBWA) threats. Inhalation and direct skin contact are common routes of exposure to CBWA. Rapid diagnostics tools against CBWA are crucial for battlefield readiness and countermeasure deployment (i.e. medical and strategic). The Defense Threat Reduction Agency is exploring the feasibility of developing novel sampling, and diagnostic tools against CBWA.

Testing for CBWA exposure using minimally invasive sample collection methods circumvents the requirement for highly trained medical personnel, anesthesia, and specialized equipment.

Minimal or non-invasive specimens such as saliva, sweat, urine, and skin are readily accessible for rapid sampling and downstream diagnostics. As an example, nasopharyngeal swabs are commonly used for detection and diagnostics of upper respiratory tract infections, do not require rigorous training, and can be incorporated in portable test kits (e.g. COVID-19 diagnostics). In contrast, traditional sampling methods to diagnose lower respiratory tract infections rely on the use of technical procedures including bronchoalveolar lavage fluid, bronchial needle brushing, and transbronchial lung biopsy1. Studies have shown that these sampling methods are more sensitive detecting lower respiratory tract infections compared to blood samples, highlighting the importance of direct tissue sampling2,3. However, these methods require trained medical personnel and anesthesia, rendering them unsuitable for rapid diagnostics in a field setting. Also, induced sputum is a non-invasive alternative for sample collection of lower respiratory tract fluids and has been used to detect bacterial and viral pathogens4,5,6,7. Nonetheless, this method is prone to false negatives and sample yields are inconsistent among patients1,4.

Objective: This topic seeks innovative solutions for minimally or non-invasive sampling technologies for the diagnosis of CBWA exposures. In addition, diagnostics tools should incorporate agnostic or multiplexed assays against these agents. Successful efforts should address any or all of the following (preference will be given to those proposals that seek to address more areas):

1. Non-invasive methods sample collection in the field.

2. Sputum sample collection that is optimized and standardized for diagnostics analyses.

3. Agnostic sensors against CBWA adaptable to portable platforms.

4. Inhalable nanosensors or small particles that could detect and report exposures to

CBWA.

5. Develop non-invasive sampling methods that indicate respiratory infections. To include but not limited to skin sampling (sweat and/or microbiome analysis), saliva sampling or ocular readings.

6. Novel detection assays, which after reacting with CBWA, release a signal or biomarker detectable by conventional specimen samples (i.e. blood, urine, saliva).

Applicants are encouraged to develop research collaborations with other Government agencies, academic institutions, and private entities. In addition, applicants can leverage resources within the Department of Defense research laboratories.

Impact: This topic will advance medical diagnostics technologies to support warfighters readiness against potential CBWA threats. These capabilities are crucial to allow rapid diagnostics following a CBWA exposure event (deliberate or natural), avoid unnecessary treatment, and prioritize appropriate medical care. In addition, the benefits of the envisioned tool will have a broader impact on general healthcare practices and could assists healthcare professional in the etiology of bacterial and viral illnesses.

References:

1Zheng, Y., et al. (2021). The Diagnostic Value of Metagenomic Next Generation Sequencing in Lower Respiratory Tract Infection. Frontiers in Cellular and Infection Microbiology; 11:694756.

2Wang, Q., et al. (2020). Optimal Specimen Type for Accurate Diagnosis of Infectious Peripheral Pulmonary Lesions by mNGS. BMC Pulmonary Medicine; 20:268.

3Chen, X., et al. (2020). Blood and Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pneumonia. Canadian Journal of Infectious Diseases and Medical Microbiology; 2020:

6839103.

4Rueda, Z.V., et al. (2022). Induced Sputum as an Adequate Clinical Specimen for the Etiological Diagnosis of Community-acquired Pneumonia (CAP) in Children and Adolescents. International Journal of Infectious Diseases; 116:348-354.

5Grant, L.R., et al. (2012). Procedures for Collection of Induced Sputum Specimens from Children.

Clinical Infectious Diseases; 54:S140-S145.

6Doughty, E., et al. (2014). Culture-independent Detection and Characterisation of Mycobacterium tuberculosis and M. africanum in Sputum Samples using Shotgun Metagenomics on a Benchtop Sequencer. PeerJ; 2:Se185.

7Branche, A.R., et al. (2014). Detection of Respiratory Viruses in Sputum from Adults by Use of Automated Multiplex PCR. Journal of Clinical Microbiology; 52 (10):3590-3596.

CBM–01

Development of a Multi-pathogen Vaccine

Background:

Exposure to biological agents, either naturally or in a deliberate release, remains a significant threat to the warfighter, and vaccination is generally regarded as the best strategy to protect from these threats. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from various pathogens, representing a paradigm shift away from the traditional single pathogen vaccine model. These multi-pathogen vaccines are highly desirable for biothreat agent vaccine applications because they simplify the manufacturing processes and reduce the number of required vaccinations, making them more cost-effective.

For warfighters, these vaccines will provide a broad protection against multiple pathogens with immediate onset of protection enabling a rapid response to biothreat encounters while in theater.

Objective:

This topic seeks to solicit proposals focused on development of a multipathogen vaccine designed to protect against multiple biological threat agents, either current or emerging threats.

Consideration will be given to proposals that include the following:

• Determination of immunogenicity

• Determination of efficacy in predictive animal models

• Determination of onset to immunity

• Determination of durability

• Determination of the maximum number of antigens that can be target in one dose delivery

• Determination of the immune response to one antigen vaccine versus multiple antigen vaccine and the ability to protect against multiple threat agents

• Safety comparisons vs traditional delivery

Impact:

This topic supports Chemical and Biological Defense Program goals by providing a prophylaxis against multiple biothreat agents, current and emerging.

CBT-01

Optimization and Scaling of Membrane Systems

Background:

Previous Dynamic Multifunctional Materials for a Second Skin (D[MS]2) proof-of-concept efforts demonstrated production of responsive functional membranes at the approximate area of 144 square inches [12” x 12”] that are compatible with continuous manufacturing and designed for single-use protection against Chemical Warfare Agents (CWAs). As the program progresses beyond the proof-of-concept phase, successful new proposals must include optimization, fabrication, scaling, and integration. The purpose of D[MS]2 is to develop dynamic multifunctional materials that are fully integrated at the molecular level to provide unparalleled chemical and biological (C/B) function upon entering into a C/B contaminated environment. There have been many recent advances in developing dynamic materials which protect against hazardous agents by exhibiting changes in physical and/or chemical properties upon reaction with an external stimulus such as applied voltage or light. The idea behind the D(MS)2 is to develop dynamic materials that exhibit multifunctional rapid responses initiated upon interaction with C/B threat agents. It is has been demonstrated that these materials are at least bi-stable and reversible and have an ability to switch between two distinct states that can be individually maintained in a power-off mode. The materials have shown to switch between a benign state corresponding to a no or low-threat environment; and they also exhibited an altered protective state corresponding to a moderate to high-threat environment. The activation of the response was tied to a desired pre-determined threshold and acted on the order of minutes. The response was discretized; in other words the response was only activated where it was needed. All stable states were regulated solely by the dynamic material and not an external control system. In this way dynamic multifunctional materials were embedded to form a smart system: a sensitive, responsive, multi-stable system that can continuously adapt to meet performance needs.

Objective:

This topic seeks to develop, as part of the D[MS]2 portfolio, an advanced membrane system capable of a stimulated protective responsive mechanism (i.e. bistable open/close states) in response to CWAs, manufactured at a scale of at least 36 inches wide.

The responsive membrane shall comply with the successes demonstrated in the previous proof-of-concept phase. For completeness, the performance objectives along with a table outlining the performance metrics, material constraints, and scaling and integration objectives are provided below:

Performance Objectives:

• The system shall be optimized to respond to one or more CWAs (H, V, and G agents), with permeation of less than 0.4% of an agent challenge of 10g/m2 in 24 hours.

• The mechanisms for pore blocking, chemical recognition, and the timing of the response should be optimized for relevant protective performance. In other words, the protective function should turn on in less than ten (10) minutes.

• Live CWA testing must be planned and budgeted in the proposal. CWA testing must be arranged by the offeror at a Department of Defense (DoD) laboratory with a CWA surety program or a DoD-certified commercial laboratory with a CWA surety program.

State Thermal and

Moisture Management

CB Mitigation Dynamics

Stimulus Overall Response

Battledress MVTR ≥ 4,000 g/m2-day

N/A Offeror define inherent protection factor

N/A

Chemical Protective MVTR ≥ 1,000 g/m2-day

HD, GD, VX

21 – 49 ºC

15 – 99 % RH

Liquid Shed agent w/ minimum environmental impact

O(minutes) Vapor

Allow permeation 0.4%

Decontamination rate .35 ug/cm2 per min

Aerosol Provide log 3 kill over 1 hour

Materials Constraints: Materials constraints are as follows:

• Any materials proposed should be polyfluoroalkyl substance (PFAS)-free.

• The impact of fabrication processing parameters on membrane construction and application (i.e., CWA permeability and/or response) shall be defined. Defect-free membranes shall be constructed in a repeatable and reproducible manner using synthetic techniques that are compatible with continuous processing. The processing parameters used for membrane incorporation into textiles for uniforms must be studied to ensure compatibility with heat, humidity, temperature, etc.

• The membrane materials must be stable during long-term storage in potentially very cold, hot, humid, or dry climates and, after storage, maintain usefulness in operational environments with similar climate extremes. The environmental extremes that will be encountered during the normal storage and use of these membrane materials are not conducive to biological catalysts and could result in their destruction, resulting in a non-responsive membrane. Therefore, DTRA is only interested in the use of non-biological catalysts for control of the open/closed membrane response. Strategies incorporating biological materials into membranes will be considered non-responsive.

Scaling and Integration Objectives: Responsive membranes should also comply with the following scaling and integration objectives:

• The performer must scale membrane production to at least 36-inches wide via continous processes

• Performers must integrate and demonstrate compatibility of the membrane with a composite that has the ability to wick water away from the skin and shed liquid from its surface.

Deliverables:

To demonstrate production-phase capability of membranes, the next generation advanced membrane system should be optimized and manufactured at a scale to produce prototype protective garments. This will facilitate advanced testing of these materials for potential integration into warfighter suits (with the assistance of government laboratories). The final deliverables will be the following:

(1) a comprehensive report on the performance and scaling of the protective fabric to suit production;

(2) delivery of ten square yards of optimized material to be made into a protective suit; and

(3) a report outlining the integration and operation of this material within the protective suit paradigm.

Proposers should focus on material solutions that offer a clear path for manufacturability into protective garments with a delivery timeline (performance period) of no longer than three (3) years.

Offerors are encouraged to develop research and development collaborations with organizations in Government, academia, and the private sector to broaden and strengthen their knowledge, experience and capabilities. Additionally, offerors are encouraged to take advantage of specialized resources in the DoD and other Government agencies, facilities, and capabilities.

Impact:

This topic will ultimately support the warfighters by providing low thermal burden protective garments that respond to CWAs and mitigate the threat. These protective garments would allow the warfighter to enter collective protection, during which time the garment would mitigate the low level threat but retain or regenerate protective capacity for reuse and allow the warfighter to return to the field.