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.
PHASE I
The objective of Phase I is to develop an iMPS or refine an existing iMPS and demonstrate that it is capable of recapitulating the immunogenicity and efficacy of an FDA-approved vaccine against a viral pathogen. The iMPS should be capable of key functions of the innate and adaptive immune systems and data outputs should be standardized to enable comparison to existing preclinical and clinical data. Success will be measured by comparing the iMPS-produced data to existing clinical data. This phase aims to establish the foundational validity of the iMPS as a reliable tool for vaccine evaluation.
PHASE II
Phase II moves beyond replicating known vaccine responses to actively forecasting the performance of new vaccines before in vivo studies or clinical trials. It will leverage the iMPS developed or refined in Phase I to predict the immunogenicity and efficacy of novel vaccine constructs against pathogens of concern for the DoD. When available, iMPS-produced data should be compared to preclinical in vitro or in vivo data. To ensure the reproducibility and consistency of results across different laboratories and users, Standard Operating Procedures (SOPs) for the operation and maintenance of the iMPS should be developed and if necessary for the operation of the iMPS, comprehensive training materials should also be created. Deliverables will be iMPS SOPs and training materials as well as standardized datasets and summary reports on each vaccine construct tested.
PHASE III DUAL USE APPLICATIONS
PHASE III: This phase focuses on broadening the iMPS's application in vaccine development. Key parameters, such as route of administration, dose optimization, and booster frequency, will be evaluated using the iMPS. Furthermore, the iMPS will be utilized in a multi-organ MPS to assess potential off-target effects of vaccine candidates. The goal is to create a comprehensive iMPS platform capable of informing critical decisions throughout the vaccine development pipeline, reducing reliance on traditional animal models, and accelerating the path to clinical trials
PHASE III DUAL USE APPLICATIONS: Beyond DoD applications, the iMPS developed may be used by commercial biotechnology companies, pharmaceutical companies, academic research labs, and public health organizations to evaluate vaccine immunogenicity and efficacy outside of an animal model, in line with FDA guidance.
REFERENCES
Morrocchi E, van Haren S, Palma P, Levy O. Modeling human immune responses to vaccination in vitro. Trends Immunol. 2024 Jan.,45(1):32-47. doi: 10.1016/j.it.2023.11.002. Epub 2023 Dec 21. PMID: 38135599., PMCID: PMC11688643.
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