19-10-MID-PIP

Military Infectious Disease – Prototype Innovation Program (MID-PIP)

The Joint Program Committee (JPC)-2/Military Infectious Disease Research Program (MIDRP) is one of six major Defense Health Program (DHP) core research program areas within the DHP medical Research Development Test & Evaluation (RDT&E). JPC-2 is a committee of Department of Defense (DoD) and non-DoD medical and military technical experts in infectious disease-related program areas. Per the program’s mission statement, JPC-2/MIDRP seeks to plan, coordinate and oversee for the DoD, a focused and responsive world class infectious diseases Science and Technology (S&T) program, leading to fielding of effective, improved means of protection and treatment to maintain effective global operational capability by maximizing Warfighter readiness and performance. This program aims to advance solutions in relation to the following focus areas:

  • A point-of-care device to detect the presence of microbial infection.
  • Generation of high affinity monoclonal antibodies to four bacterial antigens for the prevention and treatment of bacterial wound infections and sepsis
  • A single administration escape-resistant therapy for HIV control
  • Clinical evaluation of products to treat biofilm-mediated antibiotic-resistant infections in non-healing chronic wounds

 

The research project award recipients were selected from the Offerors who responded to MTEC’s Request for Project Proposals (19-10-MID-PIP).

 

 

 

Animal Testing of TIPs: A Single-Administration Escape-Resistant HIV Antiviral Therapy

Project Team: J. David Gladstone Institutes

Award Amount: $3.68M

Project Duration: 19 months

Project Objective: The project objective is to develop a novel therapeutic for treatment of HIV, specifically a prototype single-administration escape-resistant therapy for HIV control. The Objectives/Goals of this proposal are to evaluate safety and efficacy of a novel experimental HIV intervention: Therapeutic Interfering Particles (TIPs). TIPs have the predicated capacity to act as single-administration, escape-resistant therapeutics and we have demonstrated efficacy of TIPs in humanized mice. Safety will be assessed by examining dose, time of treatment, biodistribution, genotoxicity, immunotoxicity, and transmission potential of TIPs in humanized mouse models and non-human primates (NHPs). In addition, resistance of TIPs to HIV/SIV mutational escape will be assessed in vitro and in vivo. Efficacy will also be assessed in these animal models. Additionally, humanized mice will be used to assess dose, biodistribution, and genotoxicity of TIPs. established non-human primate (NHP) models for HIV infection will be used to assess these parameters as well as immunotoxicity, transmission potential, and time of treatment.

 

 

 

DispersinB® the Missing Link in Wound Care – Clinical Evaluation of DispersinB® to Treat Biofilm Mediated Antimicrobial Resistance in Non-Healing Chronic Wound Infections

Project Team: Kane Biotech

Award Amount: $2.65M

Project Duration: 30 months

Project Objective: The objective of the proposed project is to evaluate the stability, preclinical safety, clinical safety, efficacy and usability of the DispersinB® wound gel prototype. The specific aims of this project are:

  • Stability studies: Kane Biotech will conduct stability studies (accelerated and real time) on the final DispersinB® gel, examining the stability of the prototype across a range of temperatures for a minimum of 12 months.
  • Preclinical studies: Studies examining biocompatibility and toxicity of the DispersinB® prototype both in vitro and in vivo will be conducted by Charles Rivers Laboratories.
  • Proof of Concept study: Studies examining the efficacy, safety (pharmacokinetics) of DispersinB® gel in a chronic wound pig model will be conducted by Charles Rivers Laboratories
  • Clinical safety study: A human safety study will monitor safety following the application of DispersinB® gel on multiple chronic wound types. This will be a randomized open label study, conducted at the Southwest Regional Wound Care Center.
  • Usability study: A human usability study will examine the ease of using/applying/wearing the DispersinB® topical gel for end users (clinicians and wound care patients). This study will be conducted in conjunction with the safety study at the Southwest Regional Wound Care Center.

 

 

 

Evaluation of a Microneedle-Based Technology for Point-of-Care Detection of Infection Biomarkers

Project Team: University of North Carolina

Award Amount: $4.08M

Project Duration: 47 months

Project Objective: This proposal seeks to address Focus Area #1 of the Request for Project Proposals MTEC-19-10- MID-PIP by processing and characterizing a point-of-care microneedle device to detect the presence of microbial infection. are painless as well as easy to attach to the skin. Three multiplexed lateral flow assays, which will be used to detect four biomarkers each, will be connected to three microneedles for real-time monitoring of an individual’s physiological status. The microneedle device will assess “active microbial infection” status by examining levels of interleukin-6, procalcitonin, C-reactive protein. Streptococcus pneumoniae, group A Streptococcus, Campylobacter, Escherichia coli, Candida albicans enolase, influenza A, influenza B, norovirus, and respiratory syncytial virus in the interstitial fluid. Lateral flow assays benefit from requiring no power source and exhibit stability for extended periods of time at ambient temperatures. The multiplexed lateral flow assays will provide results between 5 minutes and 30 minutes. Information obtained from the device would be used to determine the status of medical readiness of deployable and/or deployed warfighters.

 

 

 

 

 

Generation of High Affinity Monoclonal Antibodies to Staphylococcus sp. and Pseudomonas sp. for the Prevention and Treatment of Bacterial Wound Infections and Sepsis

Project Team: Centivax

Award Amount: $1.84M

Project Duration: 19 months

Project Objective: Staphylococcal and Pseudomonad infections continue to pose significant treatment hurdles to infectious disease clinicians. For those in service, post traumatic injury infections, whether localized or systemic, compound already challenging situations, and a number of strategies have been suggested to counter these infection risks, including vaccination, targeted monoclonal antibodies, and topical nanobody applications. During infection both Staphylococcus and Pseudomonas species generate a variety of pathogenic toxins and virulence factors leading to morbidity; yet, in the majority of cases healthy individuals readily fight off these infections and intoxications. Such is not, however, the case in immunocompromised individuals, such as those with massive trauma, who can quickly succumb to infection. We propose generating a panel of fully humanized, high affinity monoclonal antibodies to a set of Staphylococcus and Pseudomonas toxins using phage display technology for the prevention and treatment of bacterial wound infections and sepsis in military personnel located in Role of Care 1 and 2 facilities. These antibodies will be engineered to i) be thermostable, ii) functionally active at high affinity against target, and iii) stable in human serum and resistant to degradation in formulation at various temperatures and/or lyophilized.