Microphysiological systems to Assess Pretreatment Immunogenicity and Efficacy (MAGPIE)

Objective: Develop an immune microphysiological systems (iMPS) for the evaluation and development of vaccines against high consequence pathogens. iMPS may include, but are not limited to, immune organoid, organ-tissue equivalent, microfluidic chips, or similar systems as well as single or multiple organ models. Description: The Defense Threat Reduction Agency (DTRA) Research and Development Chemical and Biological Technologies Directorate Medical division in support of the Joint Science and Technology Office (JSTO) is charged with addressing the potential threat to the armed services posed by a wide range of pathogenic and toxic agents. In support of warfighter readiness, vaccines build a defense against known and future threats. However, the development of vaccines is stymied by traditional in vitro or in vivo models, which are slow and do not fully recapitulate the complexity of the human immune system. As a result, promising preclinical data do not necessarily translate to successful human clinical trials. This disconnect inhibits rapid response against new and emerging threats to the Warfighter. iMPS have the potential to model the human immune response in vitro, providing a route to accelerated discovery and validation of medical countermeasures by offering a bridge between preclinical studies and advanced development. Successful iMPS should (1) recapitulate immunogenicity and efficacy of a known vaccine, (2) differentiate between vaccines with variable efficacy against the same threat, and (3) predict immunogenicity of novel vaccine constructs. It would also be beneficial if iMPS could evaluate the optimal vaccine dose, schedule, and route of administration as well as predict off-target effects of a vaccine. Additionally, the data output of ideal iMPS should be standardized so that they may be compared to existing animal models and/or clinical data. Eventually, iMPS would be utilized to assess vaccine immunogenicity and efficacy against DoD pathogens of concern in a high containment environment and ultimately, would greatly facilitate vaccine development and support Warfighter readiness. Keywords: Microphysiological system, New Alternative Methodologies, Medical Countermeasures, Vaccines, Immunogenicity