Dengue Human Infection Model (DHIM) Prototype Development

Purpose

This solicitation, issued by MTEC, represents a Request for Project Proposals (RPP) for MTEC support of the U.S. Army Medical Materiel Development Activity (USAMMDA) and Military Infectious Diseases Research Program (MIDRP) technology objectives. Military relevance is a critical component of proposal submission. Strategic oversight for the award(s) supported by this RPP will be provided by USAMMDA.

Dengue viruses (DENVs) are flaviviruses transmitted by infected Aedes mosquitoes that cause a clinical spectrum of human disease ranging from mild viremia to severe intravascular volume depletion and hemorrhage. Efforts are underway worldwide to develop safe, effective anti-viral drugs and vaccines against Dengue but significant technical barriers impede progress including the immunologic complexity of the disease and lack of a correlate of protection or validated animal models of disease. Consequently, medical product developers must rely primarily on the conduct of large clinical studies in endemic regions (typically in pediatric volunteers) at great expense and financial risk.

The U.S. Military Dengue Vaccine Program seeks to change this paradigm by co-developing a safe and reproducible Dengue Human Infection Model (DHIM). A successful DHIM will be a future enabling technology for DENV medical product developers and clinical researchers to: (i) test and predict efficacy of candidate vaccines, early chemoprophylaxis and anti-virals against DENV; (ii) identify and validate biomarkers of DENV disease progression for diagnosis, clinical care, or epidemiology studies; (iii) compare or otherwise cross-reference the performance of different medical technologies or modalities in a U.S. Food and Drug Administration (FDA)-regulated test and evaluation system; and (iv) elucidate the host response at the molecular level during uncomplicated DENV infection with the goals of understanding and controlling disease progression or identifying biological correlates of protection.

The DHIM represents an opportunity for consortium members and other qualified partners to reduce their overall risk during clinical development. For example, product developers may leverage the DHIM to explore pre-infection immune profiles and correlate results with post-experimental infection clinical outcomes across a range of conditions and scenarios. It also may clarify how human humoral- and/or cellular-immune responses are associated with protection against DENV disease progression, and therefore reduce the size and scope of future clinical trials and facilitate an improved use of existing laboratory animal models. In the long term, the DHIM could become a validated tool, recognized by the FDA, to fill gaps in efficacy data from field studies and subsequently expedite licensure.

Military relevance is a critical aspect of this RPP. U.S. Service Members require an FDA-approved tetravalent DENV vaccine that is >80% efficacious. Despite development efforts over several decades, a vaccine suitable for use by the US Military has not been achieved. DENV vaccine development carries significant cost and schedule risk that may be reduced by development of an FDA-regulated, reproducible, safe DHIM. Military relevance includes the health care needs of Service Members, Veterans, and/or other Military Health System (MHS) beneficiaries; consequently, military medical needs often are also applicable to the civilian population.

Points of Contact

For inquiries, please direct your correspondence to Biomedical Research Associate Chuck Hutti, Ph.D. at Chuck.Hutti@ati.org.