title: An immunologic model for rapid vaccine assessment -- a clinical trial in a test tube.
abstract: While the duration and size of human clinical trials may be difficult to reduce, there are several parameters in pre-clinical vaccine development that may be possible to further optimise. By increasing the accuracy of the models used for pre-clinical vaccine testing, it should be possible to increase the probability that any particular vaccine candidate will be successful in human trials. In addition, an improved model will allow the collection of increasingly more-informative data in pre-clinical tests, thus aiding the rational design and formulation of candidates entered into clinical evaluation. An acceleration and increase in sophistication of pre-clinical vaccine development will thus require the advent of more physiologically-accurate models of the human immune system, coupled with substantial advances in the mechanistic understanding of vaccine efficacy, achieved by using this model. We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals. An in vitro model, termed "MIMIC" (Modular IMmune In vitro Construct), was designed and developed to reflect the human immune system in a well-based format. The MIMIC System is a laboratory-based methodology that replicates the human immune system response. It is highly automated, and can be used to simulate a clinical trial for a diverse population, without putting human subjects at risk. The MIMIC System uses the circulating immune cells of individual donors to recapitulate each individual human immune response by maintaining the autonomy of the donor. Thus, an in vitro test system has been created that is functionally equivalent to the donor's own immune system and is designed to respond in a similar manner to the in vivo response.
authors.affiliation: VaxDesign Corporation, Orlando, FL 32826-2784, USA. rhigbee@vaxdesign.com
authors.forename: Russell G
authors.initials: RG
authors.lastname: Higbee
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Byers
authors.forename: Vipra
authors.initials: V
authors.lastname: Dhir
authors.forename: Donald
authors.initials: D
authors.lastname: Drake
authors.forename: Heather G
authors.initials: HG
authors.lastname: Fahlenkamp
authors.forename: Jyoti
authors.initials: J
authors.lastname: Gangur
authors.forename: Anatoly
authors.initials: A
authors.lastname: Kachurin
authors.forename: Olga
authors.initials: O
authors.lastname: Kachurina
authors.forename: Del
authors.initials: D
authors.lastname: Leistritz
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.forename: Riyaz
authors.initials: R
authors.lastname: Mehta
authors.forename: Eric
authors.initials: E
authors.lastname: Mishkin
authors.forename: Janice
authors.initials: J
authors.lastname: Moser
authors.forename: Luis
authors.initials: L
authors.lastname: Mosquera
authors.forename: Mike
authors.initials: M
authors.lastname: Nguyen
authors.forename: Robert
authors.initials: R
authors.lastname: Parkhill
authors.forename: Santosh
authors.initials: S
authors.lastname: Pawar
authors.forename: Louis
authors.initials: L
authors.lastname: Poisson
authors.forename: Guzman
authors.initials: G
authors.lastname: Sanchez-Schmitz
authors.forename: Brian
authors.initials: B
authors.lastname: Schanen
authors.forename: Inderpal
authors.initials: I
authors.lastname: Singh
authors.forename: Haifeng
authors.initials: H
authors.lastname: Song
authors.forename: Tenekua
authors.initials: T
authors.lastname: Tapia
authors.forename: William
authors.initials: W
authors.lastname: Warren
authors.forename: Vaughan
authors.initials: V
authors.lastname: Wittman
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000276:immunology*; D057166:High-Throughput Screening Assays; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D018448:Models, Immunological; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D013744:Tetanus Toxin; D014612:Vaccines