Development of in vitro technologies for evaluation of Medical CounterMeasures (MCMs)

This is a Request for Information (RFI) issued for planning purposes, as defined in FAR 15.201(e). This is NOT a solicitation for proposals, proposal abstracts, or quotations. The Department of Defense (DoD) is not seeking proposals at this time and will not accept unsolicited proposals. This notice is open to all sources. The rapid development of Medical Countermeasures (MCMs) directed against a chemical and/or biological agent is crucial to the ability of the United States to respond to a chemical/ biological attack. However, prior to administration in patients or individuals enrolled in clinical trials, the safety, efficacy and pharmacokinetics of the MCMs must be characterized first in pre-clinical studies. Current methods for obtaining this critical information for MCMs effective against biological/chemical agents rely, almost exclusively, on experimental models (in vitro and in vivo, including animal models) that frequently have limited correlation to the human condition and often do not accurately predict clinical safety, efficacy and tolerability in human. While recent technological advances have prompted substantial gains in our knowledge of the mammalian immune system, much of this progress has been made through experimentation with animal models that fail to mimic human disease or poorly predict human immunity. Our understanding of human immunity is also hindered by the obvious experimental limitations of human subjects and the lack of appropriate assay systems to evaluate human immune cells. Regarding the latter point, many researchers still utilize a well-established PBMC assay, which was developed more than 30 years ago and relies simply on the culture of unfractionated PBMC in the presence or absence of an Ag or immune-modulator, as a means of evaluating human immune responses in vitro. The primary weakness of this approach - its inability to support the sensitization of naïve antigen-specific lymphocytes- likely results from its failure to recapitulate the types of immune cell interactions that lead to these responses in vivo.